Full text data of USP14
USP14
(TGT)
[Confidence: high (present in two of the MS resources)]
Ubiquitin carboxyl-terminal hydrolase 14; 3.4.19.12 (Deubiquitinating enzyme 14; Ubiquitin thioesterase 14; Ubiquitin-specific-processing protease 14)
Ubiquitin carboxyl-terminal hydrolase 14; 3.4.19.12 (Deubiquitinating enzyme 14; Ubiquitin thioesterase 14; Ubiquitin-specific-processing protease 14)
hRBCD
IPI00219913
IPI00219913 Ubiquitin carboxyl-terminal hydrolase 14 Ubiquitin C-terminal thiolester + H2O = ubiquitin + a thiol soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00219913 Ubiquitin carboxyl-terminal hydrolase 14 Ubiquitin C-terminal thiolester + H2O = ubiquitin + a thiol soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P54578
ID UBP14_HUMAN Reviewed; 494 AA.
AC P54578; J3QRZ5; Q53XY5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 135.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 14;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 14;
DE AltName: Full=Ubiquitin thioesterase 14;
DE AltName: Full=Ubiquitin-specific-processing protease 14;
GN Name=USP14; Synonyms=TGT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RA Deshpande K.L., Katze J.R.;
RT "tRNA-guanine transglycosylase cDNA from human placenta.";
RL Submitted (AUG-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D.,
RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S.,
RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R.,
RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T.,
RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E.,
RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H.,
RA O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-308 (ISOFORM 2).
RC TISSUE=T-cell;
RA Heil O., Ebert L., Hennig S., Henze S., Radelof U., Schneider D.,
RA Korn B.;
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP INTERACTION WITH FANCC.
RX PubMed=14499622; DOI=10.1016/S0014-4827(03)00261-1;
RA Reuter T.Y., Medhurst A.L., Waisfisz Q., Zhi Y., Herterich S.,
RA Hoehn H., Gross H.J., Joenje H., Hoatlin M.E., Mathew C.G.,
RA Huber P.A.;
RT "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins
RT in transcription regulation, cell signaling, oxidative metabolism, and
RT cellular transport.";
RL Exp. Cell Res. 289:211-221(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, AND MASS
RP SPECTROMETRY.
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using
RT sequential IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [8]
RP ASSOCIATION WITH THE 26S PROTEASOME, AND FUNCTION.
RX PubMed=18162577; DOI=10.1091/mbc.E07-10-1040;
RA Koulich E., Li X., DeMartino G.N.;
RT "Relative structural and functional roles of multiple deubiquitylating
RT proteins associated with mammalian 26S proteasome.";
RL Mol. Biol. Cell 19:1072-1082(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP FUNCTION, AND INTERACTION WITH ERN1.
RX PubMed=19135427; DOI=10.1016/j.bbrc.2008.12.182;
RA Nagai A., Kadowaki H., Maruyama T., Takeda K., Nishitoh H., Ichijo H.;
RT "USP14 inhibits ER-associated degradation via interaction with
RT IRE1alpha.";
RL Biochem. Biophys. Res. Commun. 379:995-1000(2009).
RN [11]
RP INTERACTION WITH CXCR4, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19106094; DOI=10.1074/jbc.M808507200;
RA Mines M.A., Goodwin J.S., Limbird L.E., Cui F.F., Fan G.H.;
RT "Deubiquitination of CXCR4 by USP14 is critical for both CXCL12-
RT induced CXCR4 degradation and chemotaxis but not ERK activation.";
RL J. Biol. Chem. 284:5742-5752(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-449, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143 AND THR-235, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 91-494, CATALYTIC ACTIVITY,
RP AND ACTIVE SITE.
RX PubMed=16211010; DOI=10.1038/sj.emboj.7600832;
RA Hu M., Li P., Song L., Jeffrey P.D., Chenova T.A., Wilkinson K.D.,
RA Cohen R.E., Shi Y.;
RT "Structure and mechanisms of the proteasome-associated
RT deubiquitinating enzyme USP14.";
RL EMBO J. 24:3747-3756(2005).
CC -!- FUNCTION: Proteasome-associated deubiquitinase which releases
CC ubiquitin from the proteasome targeted ubiquitinated proteins.
CC Ensures the regeneration of ubiquitin at the proteasome. Is a
CC reversibly associated subunit of the proteasome and a large
CC fraction of proteasome-free protein exists within the cell.
CC Required for the degradation of the chemokine receptor CXCR4 which
CC is critical for CXCL12-induced cell chemotaxis. Serves also as a
CC physiological inhibitor of endoplasmic reticulum-associated
CC degradation (ERAD) under the non-stressed condition by inhibiting
CC the degradation of unfolded endoplasmic reticulum proteins via
CC interaction with ERN1. Indispensable for synaptic development and
CC function at neuromuscular junctions (NMJs).
CC -!- CATALYTIC ACTIVITY: Thiol-dependent hydrolysis of ester,
CC thioester, amide, peptide and isopeptide bonds formed by the C-
CC terminal Gly of ubiquitin (a 76-residue protein attached to
CC proteins as an intracellular targeting signal).
CC -!- SUBUNIT: Homodimer (Potential). Associates with the 26S
CC proteasome. Interacts with FANCC, CXCR4 and ERN1.
CC -!- INTERACTION:
CC Q08209:PPP3CA; NbExp=3; IntAct=EBI-1048016, EBI-352922;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral
CC membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P54578-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P54578-2; Sequence=VSP_047343;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP14/UBP6
CC subfamily.
CC -!- SIMILARITY: Contains 1 ubiquitin-like domain.
CC -!- CAUTION: Was originally (Ref.1) thought to be a guanine tRNA-
CC ribosyltransferase.
CC -!- SEQUENCE CAUTION:
CC Sequence=CR976282; Type=Frameshift; Positions=288;
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DR EMBL; U30888; AAB60365.1; -; mRNA.
DR EMBL; BT007183; AAP35847.1; -; mRNA.
DR EMBL; AP000845; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003556; AAH03556.1; -; mRNA.
DR EMBL; CR976282; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; G01932; G01932.
DR RefSeq; NP_001032411.1; NM_001037334.1.
DR RefSeq; NP_005142.1; NM_005151.3.
DR UniGene; Hs.464416; -.
DR UniGene; Hs.707058; -.
DR PDB; 2AYN; X-ray; 3.20 A; A/B/C=91-494.
DR PDB; 2AYO; X-ray; 3.50 A; A=91-494.
DR PDBsum; 2AYN; -.
DR PDBsum; 2AYO; -.
DR ProteinModelPortal; P54578; -.
DR SMR; P54578; 6-86, 98-483.
DR IntAct; P54578; 30.
DR MINT; MINT-3020275; -.
DR STRING; 9606.ENSP00000261601; -.
DR ChEMBL; CHEMBL1293295; -.
DR MEROPS; C19.015; -.
DR PhosphoSite; P54578; -.
DR DMDM; 1729927; -.
DR OGP; P54578; -.
DR PaxDb; P54578; -.
DR PeptideAtlas; P54578; -.
DR PRIDE; P54578; -.
DR DNASU; 9097; -.
DR Ensembl; ENST00000261601; ENSP00000261601; ENSG00000101557.
DR Ensembl; ENST00000582707; ENSP00000464447; ENSG00000101557.
DR GeneID; 9097; -.
DR KEGG; hsa:9097; -.
DR UCSC; uc002kkg.1; human.
DR CTD; 9097; -.
DR GeneCards; GC18P000148; -.
DR HGNC; HGNC:12612; USP14.
DR HPA; HPA001308; -.
DR MIM; 607274; gene.
DR neXtProt; NX_P54578; -.
DR PharmGKB; PA37238; -.
DR eggNOG; NOG286607; -.
DR HOGENOM; HOG000202292; -.
DR HOVERGEN; HBG054185; -.
DR InParanoid; P54578; -.
DR KO; K11843; -.
DR OMA; MRRELKC; -.
DR OrthoDB; EOG7F7W8H; -.
DR PhylomeDB; P54578; -.
DR EvolutionaryTrace; P54578; -.
DR GeneWiki; USP14; -.
DR GenomeRNAi; 9097; -.
DR NextBio; 34093; -.
DR PRO; PR:P54578; -.
DR ArrayExpress; P54578; -.
DR Bgee; P54578; -.
DR CleanEx; HS_USP14; -.
DR Genevestigator; P54578; -.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0004843; F:deubiquitinase activity; TAS:ProtInc.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IMP:UniProtKB.
DR GO; GO:0070628; F:proteasome binding; IDA:UniProtKB.
DR GO; GO:0008193; F:tRNA guanylyltransferase activity; TAS:ProtInc.
DR GO; GO:0004221; F:ubiquitin thiolesterase activity; IDA:UniProtKB.
DR GO; GO:0050920; P:regulation of chemotaxis; IMP:UniProtKB.
DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; IMP:UniProtKB.
DR GO; GO:0007268; P:synaptic transmission; IEA:Ensembl.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR InterPro; IPR018200; Pept_C19ubi-hydrolase_C_CS.
DR InterPro; IPR001394; Peptidase_C19/C67.
DR InterPro; IPR019954; Ubiquitin_CS.
DR InterPro; IPR000626; Ubiquitin_dom.
DR Pfam; PF00443; UCH; 1.
DR SMART; SM00213; UBQ; 1.
DR PROSITE; PS00299; UBIQUITIN_1; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
DR PROSITE; PS00972; UCH_2_1; 1.
DR PROSITE; PS00973; UCH_2_2; 1.
DR PROSITE; PS50235; UCH_2_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell membrane;
KW Complete proteome; Cytoplasm; Hydrolase; Membrane; Phosphoprotein;
KW Protease; Proteasome; Reference proteome; Thiol protease;
KW Ubl conjugation pathway.
FT CHAIN 1 494 Ubiquitin carboxyl-terminal hydrolase 14.
FT /FTId=PRO_0000080636.
FT DOMAIN 4 80 Ubiquitin-like.
FT ACT_SITE 114 114 Nucleophile (Probable).
FT ACT_SITE 435 435 Proton acceptor (By similarity).
FT MOD_RES 143 143 Phosphoserine.
FT MOD_RES 235 235 Phosphothreonine.
FT MOD_RES 449 449 N6-acetyllysine.
FT VAR_SEQ 66 100 Missing (in isoform 2).
FT /FTId=VSP_047343.
FT STRAND 110 112
FT HELIX 114 124
FT HELIX 127 134
FT STRAND 144 147
FT HELIX 148 166
FT STRAND 168 170
FT HELIX 173 182
FT HELIX 184 187
FT HELIX 200 212
FT HELIX 242 246
FT STRAND 249 260
FT STRAND 269 278
FT STRAND 280 282
FT HELIX 286 292
FT STRAND 297 301
FT TURN 303 306
FT STRAND 311 319
FT STRAND 322 329
FT STRAND 336 339
FT STRAND 351 354
FT HELIX 356 358
FT HELIX 361 366
FT TURN 367 371
FT HELIX 372 374
FT TURN 409 412
FT STRAND 416 430
FT STRAND 433 443
FT STRAND 446 451
FT STRAND 454 458
FT HELIX 460 463
FT HELIX 464 467
FT STRAND 468 472
FT STRAND 474 481
SQ SEQUENCE 494 AA; 56069 MW; E6D4679A86E9DF00 CRC64;
MPLYSVTVKW GKEKFEGVEL NTDEPPMVFK AQLFALTGVQ PARQKVMVKG GTLKDDDWGN
IKIKNGMTLL MMGSADALPE EPSAKTVFVE DMTEEQLASA MELPCGLTNL GNTCYMNATV
QCIRSVPELK DALKRYAGAL RASGEMASAQ YITAALRDLF DSMDKTSSSI PPIILLQFLH
MAFPQFAEKG EQGQYLQQDA NECWIQMMRV LQQKLEAIED DSVKETDSSS ASAATPSKKK
SLIDQFFGVE FETTMKCTES EEEEVTKGKE NQLQLSCFIN QEVKYLFTGL KLRLQEEITK
QSPTLQRNAL YIKSSKISRL PAYLTIQMVR FFYKEKESVN AKVLKDVKFP LMLDMYELCT
PELQEKMVSF RSKFKDLEDK KVNQQPNTSD KKSSPQKEVK YEPFSFADDI GSNNCGYYDL
QAVLTHQGRS SSSGHYVSWV KRKQDEWIKF DDDKVSIVTP EDILRLSGGG DWHIAYVLLY
GPRRVEIMEE ESEQ
//
ID UBP14_HUMAN Reviewed; 494 AA.
AC P54578; J3QRZ5; Q53XY5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 135.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 14;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 14;
DE AltName: Full=Ubiquitin thioesterase 14;
DE AltName: Full=Ubiquitin-specific-processing protease 14;
GN Name=USP14; Synonyms=TGT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RA Deshpande K.L., Katze J.R.;
RT "tRNA-guanine transglycosylase cDNA from human placenta.";
RL Submitted (AUG-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D.,
RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S.,
RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R.,
RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T.,
RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E.,
RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H.,
RA O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-308 (ISOFORM 2).
RC TISSUE=T-cell;
RA Heil O., Ebert L., Hennig S., Henze S., Radelof U., Schneider D.,
RA Korn B.;
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP INTERACTION WITH FANCC.
RX PubMed=14499622; DOI=10.1016/S0014-4827(03)00261-1;
RA Reuter T.Y., Medhurst A.L., Waisfisz Q., Zhi Y., Herterich S.,
RA Hoehn H., Gross H.J., Joenje H., Hoatlin M.E., Mathew C.G.,
RA Huber P.A.;
RT "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins
RT in transcription regulation, cell signaling, oxidative metabolism, and
RT cellular transport.";
RL Exp. Cell Res. 289:211-221(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, AND MASS
RP SPECTROMETRY.
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using
RT sequential IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [8]
RP ASSOCIATION WITH THE 26S PROTEASOME, AND FUNCTION.
RX PubMed=18162577; DOI=10.1091/mbc.E07-10-1040;
RA Koulich E., Li X., DeMartino G.N.;
RT "Relative structural and functional roles of multiple deubiquitylating
RT proteins associated with mammalian 26S proteasome.";
RL Mol. Biol. Cell 19:1072-1082(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP FUNCTION, AND INTERACTION WITH ERN1.
RX PubMed=19135427; DOI=10.1016/j.bbrc.2008.12.182;
RA Nagai A., Kadowaki H., Maruyama T., Takeda K., Nishitoh H., Ichijo H.;
RT "USP14 inhibits ER-associated degradation via interaction with
RT IRE1alpha.";
RL Biochem. Biophys. Res. Commun. 379:995-1000(2009).
RN [11]
RP INTERACTION WITH CXCR4, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19106094; DOI=10.1074/jbc.M808507200;
RA Mines M.A., Goodwin J.S., Limbird L.E., Cui F.F., Fan G.H.;
RT "Deubiquitination of CXCR4 by USP14 is critical for both CXCL12-
RT induced CXCR4 degradation and chemotaxis but not ERK activation.";
RL J. Biol. Chem. 284:5742-5752(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-449, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143 AND THR-235, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 91-494, CATALYTIC ACTIVITY,
RP AND ACTIVE SITE.
RX PubMed=16211010; DOI=10.1038/sj.emboj.7600832;
RA Hu M., Li P., Song L., Jeffrey P.D., Chenova T.A., Wilkinson K.D.,
RA Cohen R.E., Shi Y.;
RT "Structure and mechanisms of the proteasome-associated
RT deubiquitinating enzyme USP14.";
RL EMBO J. 24:3747-3756(2005).
CC -!- FUNCTION: Proteasome-associated deubiquitinase which releases
CC ubiquitin from the proteasome targeted ubiquitinated proteins.
CC Ensures the regeneration of ubiquitin at the proteasome. Is a
CC reversibly associated subunit of the proteasome and a large
CC fraction of proteasome-free protein exists within the cell.
CC Required for the degradation of the chemokine receptor CXCR4 which
CC is critical for CXCL12-induced cell chemotaxis. Serves also as a
CC physiological inhibitor of endoplasmic reticulum-associated
CC degradation (ERAD) under the non-stressed condition by inhibiting
CC the degradation of unfolded endoplasmic reticulum proteins via
CC interaction with ERN1. Indispensable for synaptic development and
CC function at neuromuscular junctions (NMJs).
CC -!- CATALYTIC ACTIVITY: Thiol-dependent hydrolysis of ester,
CC thioester, amide, peptide and isopeptide bonds formed by the C-
CC terminal Gly of ubiquitin (a 76-residue protein attached to
CC proteins as an intracellular targeting signal).
CC -!- SUBUNIT: Homodimer (Potential). Associates with the 26S
CC proteasome. Interacts with FANCC, CXCR4 and ERN1.
CC -!- INTERACTION:
CC Q08209:PPP3CA; NbExp=3; IntAct=EBI-1048016, EBI-352922;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral
CC membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P54578-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P54578-2; Sequence=VSP_047343;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP14/UBP6
CC subfamily.
CC -!- SIMILARITY: Contains 1 ubiquitin-like domain.
CC -!- CAUTION: Was originally (Ref.1) thought to be a guanine tRNA-
CC ribosyltransferase.
CC -!- SEQUENCE CAUTION:
CC Sequence=CR976282; Type=Frameshift; Positions=288;
CC -----------------------------------------------------------------------
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DR EMBL; U30888; AAB60365.1; -; mRNA.
DR EMBL; BT007183; AAP35847.1; -; mRNA.
DR EMBL; AP000845; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003556; AAH03556.1; -; mRNA.
DR EMBL; CR976282; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; G01932; G01932.
DR RefSeq; NP_001032411.1; NM_001037334.1.
DR RefSeq; NP_005142.1; NM_005151.3.
DR UniGene; Hs.464416; -.
DR UniGene; Hs.707058; -.
DR PDB; 2AYN; X-ray; 3.20 A; A/B/C=91-494.
DR PDB; 2AYO; X-ray; 3.50 A; A=91-494.
DR PDBsum; 2AYN; -.
DR PDBsum; 2AYO; -.
DR ProteinModelPortal; P54578; -.
DR SMR; P54578; 6-86, 98-483.
DR IntAct; P54578; 30.
DR MINT; MINT-3020275; -.
DR STRING; 9606.ENSP00000261601; -.
DR ChEMBL; CHEMBL1293295; -.
DR MEROPS; C19.015; -.
DR PhosphoSite; P54578; -.
DR DMDM; 1729927; -.
DR OGP; P54578; -.
DR PaxDb; P54578; -.
DR PeptideAtlas; P54578; -.
DR PRIDE; P54578; -.
DR DNASU; 9097; -.
DR Ensembl; ENST00000261601; ENSP00000261601; ENSG00000101557.
DR Ensembl; ENST00000582707; ENSP00000464447; ENSG00000101557.
DR GeneID; 9097; -.
DR KEGG; hsa:9097; -.
DR UCSC; uc002kkg.1; human.
DR CTD; 9097; -.
DR GeneCards; GC18P000148; -.
DR HGNC; HGNC:12612; USP14.
DR HPA; HPA001308; -.
DR MIM; 607274; gene.
DR neXtProt; NX_P54578; -.
DR PharmGKB; PA37238; -.
DR eggNOG; NOG286607; -.
DR HOGENOM; HOG000202292; -.
DR HOVERGEN; HBG054185; -.
DR InParanoid; P54578; -.
DR KO; K11843; -.
DR OMA; MRRELKC; -.
DR OrthoDB; EOG7F7W8H; -.
DR PhylomeDB; P54578; -.
DR EvolutionaryTrace; P54578; -.
DR GeneWiki; USP14; -.
DR GenomeRNAi; 9097; -.
DR NextBio; 34093; -.
DR PRO; PR:P54578; -.
DR ArrayExpress; P54578; -.
DR Bgee; P54578; -.
DR CleanEx; HS_USP14; -.
DR Genevestigator; P54578; -.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0004843; F:deubiquitinase activity; TAS:ProtInc.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IMP:UniProtKB.
DR GO; GO:0070628; F:proteasome binding; IDA:UniProtKB.
DR GO; GO:0008193; F:tRNA guanylyltransferase activity; TAS:ProtInc.
DR GO; GO:0004221; F:ubiquitin thiolesterase activity; IDA:UniProtKB.
DR GO; GO:0050920; P:regulation of chemotaxis; IMP:UniProtKB.
DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; IMP:UniProtKB.
DR GO; GO:0007268; P:synaptic transmission; IEA:Ensembl.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR InterPro; IPR018200; Pept_C19ubi-hydrolase_C_CS.
DR InterPro; IPR001394; Peptidase_C19/C67.
DR InterPro; IPR019954; Ubiquitin_CS.
DR InterPro; IPR000626; Ubiquitin_dom.
DR Pfam; PF00443; UCH; 1.
DR SMART; SM00213; UBQ; 1.
DR PROSITE; PS00299; UBIQUITIN_1; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
DR PROSITE; PS00972; UCH_2_1; 1.
DR PROSITE; PS00973; UCH_2_2; 1.
DR PROSITE; PS50235; UCH_2_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell membrane;
KW Complete proteome; Cytoplasm; Hydrolase; Membrane; Phosphoprotein;
KW Protease; Proteasome; Reference proteome; Thiol protease;
KW Ubl conjugation pathway.
FT CHAIN 1 494 Ubiquitin carboxyl-terminal hydrolase 14.
FT /FTId=PRO_0000080636.
FT DOMAIN 4 80 Ubiquitin-like.
FT ACT_SITE 114 114 Nucleophile (Probable).
FT ACT_SITE 435 435 Proton acceptor (By similarity).
FT MOD_RES 143 143 Phosphoserine.
FT MOD_RES 235 235 Phosphothreonine.
FT MOD_RES 449 449 N6-acetyllysine.
FT VAR_SEQ 66 100 Missing (in isoform 2).
FT /FTId=VSP_047343.
FT STRAND 110 112
FT HELIX 114 124
FT HELIX 127 134
FT STRAND 144 147
FT HELIX 148 166
FT STRAND 168 170
FT HELIX 173 182
FT HELIX 184 187
FT HELIX 200 212
FT HELIX 242 246
FT STRAND 249 260
FT STRAND 269 278
FT STRAND 280 282
FT HELIX 286 292
FT STRAND 297 301
FT TURN 303 306
FT STRAND 311 319
FT STRAND 322 329
FT STRAND 336 339
FT STRAND 351 354
FT HELIX 356 358
FT HELIX 361 366
FT TURN 367 371
FT HELIX 372 374
FT TURN 409 412
FT STRAND 416 430
FT STRAND 433 443
FT STRAND 446 451
FT STRAND 454 458
FT HELIX 460 463
FT HELIX 464 467
FT STRAND 468 472
FT STRAND 474 481
SQ SEQUENCE 494 AA; 56069 MW; E6D4679A86E9DF00 CRC64;
MPLYSVTVKW GKEKFEGVEL NTDEPPMVFK AQLFALTGVQ PARQKVMVKG GTLKDDDWGN
IKIKNGMTLL MMGSADALPE EPSAKTVFVE DMTEEQLASA MELPCGLTNL GNTCYMNATV
QCIRSVPELK DALKRYAGAL RASGEMASAQ YITAALRDLF DSMDKTSSSI PPIILLQFLH
MAFPQFAEKG EQGQYLQQDA NECWIQMMRV LQQKLEAIED DSVKETDSSS ASAATPSKKK
SLIDQFFGVE FETTMKCTES EEEEVTKGKE NQLQLSCFIN QEVKYLFTGL KLRLQEEITK
QSPTLQRNAL YIKSSKISRL PAYLTIQMVR FFYKEKESVN AKVLKDVKFP LMLDMYELCT
PELQEKMVSF RSKFKDLEDK KVNQQPNTSD KKSSPQKEVK YEPFSFADDI GSNNCGYYDL
QAVLTHQGRS SSSGHYVSWV KRKQDEWIKF DDDKVSIVTP EDILRLSGGG DWHIAYVLLY
GPRRVEIMEE ESEQ
//
MIM
607274
*RECORD*
*FIELD* NO
607274
*FIELD* TI
*607274 UBIQUITIN-SPECIFIC PROTEASE 14; USP14
;;tRNA-GUANINE TRANSGLYCOSYLASE, 60-KD SUBUNIT;;
read moreTGT, 60-KD SUBUNIT
*FIELD* TX
CLONING
Eukaryotes synthesize queuosine by the irreversible exchange of queuine
for guanine at tRNA position 34, a reaction catalyzed by tRNA-guanine
transglycosylase (TGT). Mammalian TGT appears to be a dimer of 60- and
43-kD subunits. Deshpande et al. (1996) determined that the purified
rabbit 60-kD Tgt subunit, or Usp14, shares significant sequence identity
with human TRE2 (USP6; 604334) and ORF8 (USP8; 603158), particularly in
the conserved cys and his domains. Using the rabbit sequence, they
identified an EST containing human USP14 and cloned the cDNA from a
placenta cDNA library. The deduced human protein contains 494 amino
acids and shares 98% sequence identity with the rabbit protein.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the USP14
gene to chromosome 18 (TMAP SJGC-11272). Wilson et al. (2002) stated
that 2 human neurologic disorders possibly involving alterations of
synaptic function map to 18p near USP14: major affective disorder-1
(MAFD1; 125480) and schizophrenia disorder 8 (SCZD8; 603206).
GENE FUNCTION
Lee et al. (2010) showed that USP14, a proteasome-associated
deubiquitinating enzyme, can inhibit the degradation of
ubiquitin-protein conjugates both in vitro and in vivo and in cells. A
catalytically inactive variant of USP14 has reduced inhibitory activity,
indicating that inhibition is mediated by trimming of the ubiquitin
chain on the substrate. A high-throughput screen identified a selective
small-molecule inhibitor of the deubiquitinating activity of human
USP14. Treatment of cultured cells with this compound enhanced
degradation of several proteasome substrates that have been implicated
in neurodegenerative disease. USP14 inhibition accelerated the
degradation of oxidized proteins and enhanced resistance to oxidative
stress.
ANIMAL MODEL
Mice that are homozygous with respect to the spontaneous mutation ax(J)
in the ataxia (ax) gene develop severe tremors by 2 to 3 weeks of age
followed by hindlimb paralysis and death by 6 to 10 weeks of age. Wilson
et al. (2002) showed that ax encodes Usp14, one of the large family of
cysteine proteases that specifically feed ubiquitin conjugates. Although
Usp14 can cleave a ubiquitin-tagged protein in vitro, it is unable to
process polyubiquitin, which is believed to be associated with the
protein aggregates seen in Parkinson disease, spinocerebellar ataxia
type 1 (SCA1; 164400), and gracile axonal dystrophy (GAD) in mice. The
physiologic substrate of Usp14 may therefore contain a monoubiquitin
side chain, the removal of which would regulate processes such as
protein localization and protein activity. Expression of Usp14 is
altered in homozygous ax(J) mice as a result of the insertion of an
intracisternal A particle (IAP) into intron 5 of Usp14. In contrast to
other neurodegenerative disorders such as Parkinson disease and SCA1 in
humans and GAD in mice, neither ubiquitin-positive protein aggregates
nor neuronal cell loss was detectable in the CNS of ax(J) mice. Instead,
these mice had defects in synaptic transmission in both the central and
peripheral nervous systems. These results suggested that ubiquitin
proteases are important in regulating synaptic activity in mammals.
*FIELD* RF
1. Deshpande, K. L.; Seubert, P. H.; Tillman, D. M.; Farkas, W. R.;
Katze, J. R.: Cloning and characterization of cDNA encoding the rabbit
tRNA-guanine transglycosylase 60-kilodalton subunit. Arch. Biochem.
Biophys. 326: 1-7, 1996.
2. Lee, B.-H.; Lee, M. J.; Park, S.; Oh, D.-C.; Elsasser, S.; Chen,
P.-C.; Gartner, C.; Dimova, N.; Hanna, J.; Gygi, S. P.; Wilson, S.
M.; King, R. W.; Finley, D.: Enhancement of proteasome activity by
a small-molecule inhibitor of USP14. Nature 467: 179-184, 2010.
3. Wilson, S. M.; Bhattacharyya, B.; Rachel, R. A.; Coppola, V.; Tessarollo,
L.; Householder, D. B.; Fletcher, C. F.; Miller, R. J.; Copeland,
N. G.; Jenkins, N. A.: Synaptic defects in ataxia mice result from
a mutation in Usp14, encoding a ubiquitin-specific protease. Nature
Genet. 32: 420-425, 2002.
*FIELD* CN
Ada Hamosh - updated: 10/6/2010
*FIELD* CD
Patricia A. Hartz: 10/3/2002
*FIELD* ED
alopez: 10/06/2010
terry: 10/6/2010
mgross: 9/28/2005
alopez: 11/7/2002
cwells: 10/7/2002
terry: 10/4/2002
mgross: 10/3/2002
*RECORD*
*FIELD* NO
607274
*FIELD* TI
*607274 UBIQUITIN-SPECIFIC PROTEASE 14; USP14
;;tRNA-GUANINE TRANSGLYCOSYLASE, 60-KD SUBUNIT;;
read moreTGT, 60-KD SUBUNIT
*FIELD* TX
CLONING
Eukaryotes synthesize queuosine by the irreversible exchange of queuine
for guanine at tRNA position 34, a reaction catalyzed by tRNA-guanine
transglycosylase (TGT). Mammalian TGT appears to be a dimer of 60- and
43-kD subunits. Deshpande et al. (1996) determined that the purified
rabbit 60-kD Tgt subunit, or Usp14, shares significant sequence identity
with human TRE2 (USP6; 604334) and ORF8 (USP8; 603158), particularly in
the conserved cys and his domains. Using the rabbit sequence, they
identified an EST containing human USP14 and cloned the cDNA from a
placenta cDNA library. The deduced human protein contains 494 amino
acids and shares 98% sequence identity with the rabbit protein.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the USP14
gene to chromosome 18 (TMAP SJGC-11272). Wilson et al. (2002) stated
that 2 human neurologic disorders possibly involving alterations of
synaptic function map to 18p near USP14: major affective disorder-1
(MAFD1; 125480) and schizophrenia disorder 8 (SCZD8; 603206).
GENE FUNCTION
Lee et al. (2010) showed that USP14, a proteasome-associated
deubiquitinating enzyme, can inhibit the degradation of
ubiquitin-protein conjugates both in vitro and in vivo and in cells. A
catalytically inactive variant of USP14 has reduced inhibitory activity,
indicating that inhibition is mediated by trimming of the ubiquitin
chain on the substrate. A high-throughput screen identified a selective
small-molecule inhibitor of the deubiquitinating activity of human
USP14. Treatment of cultured cells with this compound enhanced
degradation of several proteasome substrates that have been implicated
in neurodegenerative disease. USP14 inhibition accelerated the
degradation of oxidized proteins and enhanced resistance to oxidative
stress.
ANIMAL MODEL
Mice that are homozygous with respect to the spontaneous mutation ax(J)
in the ataxia (ax) gene develop severe tremors by 2 to 3 weeks of age
followed by hindlimb paralysis and death by 6 to 10 weeks of age. Wilson
et al. (2002) showed that ax encodes Usp14, one of the large family of
cysteine proteases that specifically feed ubiquitin conjugates. Although
Usp14 can cleave a ubiquitin-tagged protein in vitro, it is unable to
process polyubiquitin, which is believed to be associated with the
protein aggregates seen in Parkinson disease, spinocerebellar ataxia
type 1 (SCA1; 164400), and gracile axonal dystrophy (GAD) in mice. The
physiologic substrate of Usp14 may therefore contain a monoubiquitin
side chain, the removal of which would regulate processes such as
protein localization and protein activity. Expression of Usp14 is
altered in homozygous ax(J) mice as a result of the insertion of an
intracisternal A particle (IAP) into intron 5 of Usp14. In contrast to
other neurodegenerative disorders such as Parkinson disease and SCA1 in
humans and GAD in mice, neither ubiquitin-positive protein aggregates
nor neuronal cell loss was detectable in the CNS of ax(J) mice. Instead,
these mice had defects in synaptic transmission in both the central and
peripheral nervous systems. These results suggested that ubiquitin
proteases are important in regulating synaptic activity in mammals.
*FIELD* RF
1. Deshpande, K. L.; Seubert, P. H.; Tillman, D. M.; Farkas, W. R.;
Katze, J. R.: Cloning and characterization of cDNA encoding the rabbit
tRNA-guanine transglycosylase 60-kilodalton subunit. Arch. Biochem.
Biophys. 326: 1-7, 1996.
2. Lee, B.-H.; Lee, M. J.; Park, S.; Oh, D.-C.; Elsasser, S.; Chen,
P.-C.; Gartner, C.; Dimova, N.; Hanna, J.; Gygi, S. P.; Wilson, S.
M.; King, R. W.; Finley, D.: Enhancement of proteasome activity by
a small-molecule inhibitor of USP14. Nature 467: 179-184, 2010.
3. Wilson, S. M.; Bhattacharyya, B.; Rachel, R. A.; Coppola, V.; Tessarollo,
L.; Householder, D. B.; Fletcher, C. F.; Miller, R. J.; Copeland,
N. G.; Jenkins, N. A.: Synaptic defects in ataxia mice result from
a mutation in Usp14, encoding a ubiquitin-specific protease. Nature
Genet. 32: 420-425, 2002.
*FIELD* CN
Ada Hamosh - updated: 10/6/2010
*FIELD* CD
Patricia A. Hartz: 10/3/2002
*FIELD* ED
alopez: 10/06/2010
terry: 10/6/2010
mgross: 9/28/2005
alopez: 11/7/2002
cwells: 10/7/2002
terry: 10/4/2002
mgross: 10/3/2002