Full text data of UCHL5
UCHL5
(UCH37)
[Confidence: low (only semi-automatic identification from reviews)]
Ubiquitin carboxyl-terminal hydrolase isozyme L5; UCH-L5; 3.4.19.12 (Ubiquitin C-terminal hydrolase UCH37; Ubiquitin thioesterase L5)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ubiquitin carboxyl-terminal hydrolase isozyme L5; UCH-L5; 3.4.19.12 (Ubiquitin C-terminal hydrolase UCH37; Ubiquitin thioesterase L5)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9Y5K5
ID UCHL5_HUMAN Reviewed; 329 AA.
AC Q9Y5K5; Q5LJA6; Q5LJA7; Q8TBS4; Q96BJ9; Q9H1W5; Q9P0I3; Q9UQN2;
read moreDT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 3.
DT 22-JAN-2014, entry version 120.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase isozyme L5;
DE Short=UCH-L5;
DE EC=3.4.19.12;
DE AltName: Full=Ubiquitin C-terminal hydrolase UCH37;
DE AltName: Full=Ubiquitin thioesterase L5;
GN Name=UCHL5; Synonyms=UCH37; ORFNames=AD-019, CGI-70;
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), FUNCTION, ENZYME REGULATION,
RP MUTAGENESIS OF CYS-88, AND INTERACTION WITH ADRM1.
RX PubMed=16906146; DOI=10.1038/ncb1460;
RA Yao T., Song L., Xu W., DeMartino G.N., Florens L., Swanson S.K.,
RA Washburn M.P., Conaway R.C., Conaway J.W., Cohen R.E.;
RT "Proteasome recruitment and activation of the Uch37 deubiquitinating
RT enzyme by Adrm1.";
RL Nat. Cell Biol. 8:994-1002(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT
RP PHE-197.
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT
RP PHE-197.
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Lung, and Uterus;
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 [7]
RP INTERACTION WITH ADRM1, AND MASS SPECTROMETRY.
RX PubMed=16990800; DOI=10.1038/sj.emboj.7601338;
RA Hamazaki J., Iemura S., Natsume T., Yashiroda H., Tanaka K.,
RA Murata S.;
RT "A novel proteasome-interacting protein recruits the deubiquitinating
RT enzyme UCH37 to 26S proteasomes.";
RL EMBO J. 25:4524-4536(2006).
RN [8]
RP INTERACTION WITH ADRM1, ENZYME REGULATION, AND MASS SPECTROMETRY.
RX PubMed=17139257; DOI=10.1038/sj.emboj.7601450;
RA Qiu X.-B., Ouyang S.-Y., Li C.-J., Miao S., Wang L., Goldberg A.L.;
RT "hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds the
RT deubiquitinating enzyme, UCH37.";
RL EMBO J. 25:5742-5753(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17323924; DOI=10.1021/bi061994u;
RA Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L.;
RT "Mass spectrometric characterization of the affinity-purified human
RT 26S proteasome complex.";
RL Biochemistry 46:3553-3565(2007).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, IDENTIFICATION IN THE INO80
RP COMPLEX, INTERACTION WITH NFRKB AND ADRM1, AND ENZYME REGULATION.
RX PubMed=18922472; DOI=10.1016/j.molcel.2008.08.027;
RA Yao T., Song L., Jin J., Cai Y., Takahashi H., Swanson S.K.,
RA Washburn M.P., Florens L., Conaway R.C., Cohen R.E., Conaway J.W.;
RT "Distinct modes of regulation of the Uch37 deubiquitinating enzyme in
RT the proteasome and in the Ino80 chromatin-remodeling complex.";
RL Mol. Cell 31:909-917(2008).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-158, 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 [12]
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 [13]
RP IDENTIFICATION IN THE INO80 COMPLEX.
RX PubMed=21303910; DOI=10.1074/jbc.M111.222505;
RA Chen L., Cai Y., Jin J., Florens L., Swanson S.K., Washburn M.P.,
RA Conaway J.W., Conaway R.C.;
RT "Subunit organization of the human INO80 chromatin remodeling complex:
RT An evolutionarily conserved core complex catalyzes ATP-dependent
RT nucleosome remodeling.";
RL J. Biol. Chem. 286:11283-11289(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-228.
RX PubMed=19836345; DOI=10.1016/j.bbrc.2009.10.062;
RA Nishio K., Kim S.W., Kawai K., Mizushima T., Yamane T., Hamazaki J.,
RA Murata S., Tanaka K., Morimoto Y.;
RT "Crystal structure of the de-ubiquitinating enzyme UCH37 (human UCH-
RT L5) catalytic domain.";
RL Biochem. Biophys. Res. Commun. 390:855-860(2009).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 2-328.
RG Center for eukaryotic structural genomics (CESG);
RT "Crystal structure of UCH37.";
RL Submitted (AUG-2009) to the PDB data bank.
CC -!- FUNCTION: Protease that specifically cleaves 'Lys-48'-linked
CC polyubiquitin chains. Deubiquitinating enzyme associated with the
CC 19S regulatory subunit of the 26S proteasome. Putative regulatory
CC component of the INO80 complex; however is inactive in the INO80
CC complex and is activated by a transient interaction of the INO80
CC complex with the proteasome via ADRM1.
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 -!- ENZYME REGULATION: Activated by ADRM1. Inhibited by interaction
CC with NFRKB.
CC -!- SUBUNIT: Component of the 19S (PA700) regulatory complex of the
CC 26S proteasome. Interacts with ADRM1 and NFRKB; in vitro ADRM1 and
CC NFRKB compete for interaction with UCHL5. Component of the INO80
CC complex; specifically part of a complex module associated with N-
CC terminus of INO80.
CC -!- INTERACTION:
CC Q9H981:ACTR8; NbExp=3; IntAct=EBI-1051183, EBI-769597;
CC Q16186:ADRM1; NbExp=17; IntAct=EBI-1051183, EBI-954387;
CC Q8NBZ0:INO80E; NbExp=7; IntAct=EBI-1051183, EBI-769401;
CC Q6P4R8:NFRKB; NbExp=9; IntAct=EBI-1051183, EBI-2511210;
CC P60900:PSMA6; NbExp=4; IntAct=EBI-1051183, EBI-357793;
CC Q13200:PSMD2; NbExp=5; IntAct=EBI-1051183, EBI-357648;
CC P55036:PSMD4; NbExp=5; IntAct=EBI-1051183, EBI-359318;
CC P0C1Z6:TFPT; NbExp=3; IntAct=EBI-1051183, EBI-1245626;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Associates with the
CC proteasome 19S subunit in the cytoplasm. Associates with the INO80
CC complex in the nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Experimental confirmation may be lacking for some
CC isoforms;
CC Name=1;
CC IsoId=Q9Y5K5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y5K5-2; Sequence=VSP_005253, VSP_005254;
CC Name=3;
CC IsoId=Q9Y5K5-3; Sequence=VSP_005253;
CC Name=4;
CC IsoId=Q9Y5K5-4; Sequence=VSP_005253, VSP_017062;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the peptidase C12 family.
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DR EMBL; AF147717; AAD31528.1; -; mRNA.
DR EMBL; AF151828; AAD34065.1; -; mRNA.
DR EMBL; AF157320; AAF67486.1; -; mRNA.
DR EMBL; BT006790; AAP35436.1; -; mRNA.
DR EMBL; AL136370; CAI10829.1; -; Genomic_DNA.
DR EMBL; AL136370; CAI10830.1; -; Genomic_DNA.
DR EMBL; AL136370; CAI10831.1; -; Genomic_DNA.
DR EMBL; AL136370; CAI10833.1; -; Genomic_DNA.
DR EMBL; BC015521; AAH15521.1; -; mRNA.
DR EMBL; BC025369; AAH25369.1; -; mRNA.
DR RefSeq; NP_001186190.1; NM_001199261.1.
DR RefSeq; NP_001186191.1; NM_001199262.1.
DR RefSeq; NP_001186192.1; NM_001199263.1.
DR RefSeq; NP_057068.1; NM_015984.3.
DR UniGene; Hs.145469; -.
DR PDB; 3A7S; X-ray; 2.20 A; A=1-228.
DR PDB; 3IHR; X-ray; 2.95 A; A=2-329.
DR PDB; 3RII; X-ray; 2.00 A; A/B=1-228.
DR PDB; 3RIS; X-ray; 2.40 A; A/B/C/D=1-240.
DR PDB; 3TB3; X-ray; 2.30 A; A/B=1-227.
DR PDBsum; 3A7S; -.
DR PDBsum; 3IHR; -.
DR PDBsum; 3RII; -.
DR PDBsum; 3RIS; -.
DR PDBsum; 3TB3; -.
DR ProteinModelPortal; Q9Y5K5; -.
DR SMR; Q9Y5K5; 7-312.
DR DIP; DIP-42671N; -.
DR IntAct; Q9Y5K5; 58.
DR MINT; MINT-2823912; -.
DR STRING; 9606.ENSP00000356425; -.
DR MEROPS; C12.005; -.
DR PhosphoSite; Q9Y5K5; -.
DR DMDM; 108936023; -.
DR PaxDb; Q9Y5K5; -.
DR PRIDE; Q9Y5K5; -.
DR DNASU; 51377; -.
DR Ensembl; ENST00000367448; ENSP00000356418; ENSG00000116750.
DR Ensembl; ENST00000367449; ENSP00000356419; ENSG00000116750.
DR Ensembl; ENST00000367454; ENSP00000356424; ENSG00000116750.
DR Ensembl; ENST00000367455; ENSP00000356425; ENSG00000116750.
DR GeneID; 51377; -.
DR KEGG; hsa:51377; -.
DR UCSC; uc001gsm.3; human.
DR CTD; 51377; -.
DR GeneCards; GC01M192984; -.
DR HGNC; HGNC:19678; UCHL5.
DR HPA; HPA005908; -.
DR MIM; 610667; gene.
DR neXtProt; NX_Q9Y5K5; -.
DR PharmGKB; PA134916228; -.
DR eggNOG; NOG321645; -.
DR HOVERGEN; HBG056021; -.
DR KO; K05610; -.
DR PhylomeDB; Q9Y5K5; -.
DR BRENDA; 3.4.19.12; 2681.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR SignaLink; Q9Y5K5; -.
DR ChiTaRS; UCHL5; human.
DR EvolutionaryTrace; Q9Y5K5; -.
DR GeneWiki; Ubiquitin_carboxyl-terminal_hydrolase_L5; -.
DR GenomeRNAi; 51377; -.
DR NextBio; 54875; -.
DR PRO; PR:Q9Y5K5; -.
DR ArrayExpress; Q9Y5K5; -.
DR Bgee; Q9Y5K5; -.
DR CleanEx; HS_UCHL5; -.
DR Genevestigator; Q9Y5K5; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031011; C:Ino80 complex; IDA:UniProtKB.
DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW.
DR GO; GO:0004843; F:deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IMP:UniProtKB.
DR GO; GO:0008242; F:omega peptidase activity; IEA:InterPro.
DR GO; GO:0070628; F:proteasome binding; IDA:UniProtKB.
DR GO; GO:0004221; F:ubiquitin thiolesterase activity; IEA:InterPro.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0048853; P:forebrain morphogenesis; IEA:Ensembl.
DR GO; GO:0021670; P:lateral ventricle development; IEA:Ensembl.
DR GO; GO:0030901; P:midbrain development; IEA:Ensembl.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:Reactome.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.40.532.10; -; 1.
DR InterPro; IPR001578; Peptidase_C12.
DR InterPro; IPR017390; Ubiquitinyl_hydrolase_UCH37.
DR PANTHER; PTHR10589; PTHR10589; 1.
DR Pfam; PF01088; Peptidase_C12; 1.
DR PIRSF; PIRSF038120; Ubiquitinyl_hydrolase_UCH37; 1.
DR PRINTS; PR00707; UBCTHYDRLASE.
DR PROSITE; PS00140; UCH_1; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; DNA damage; DNA recombination; DNA repair; Hydrolase;
KW Nucleus; Polymorphism; Protease; Proteasome; Reference proteome;
KW Thiol protease; Transcription; Transcription regulation;
KW Ubl conjugation pathway.
FT CHAIN 1 329 Ubiquitin carboxyl-terminal hydrolase
FT isozyme L5.
FT /FTId=PRO_0000211066.
FT REGION 313 329 Interaction with ADRM1.
FT ACT_SITE 88 88 Nucleophile (Probable).
FT ACT_SITE 164 164 Proton donor (By similarity).
FT SITE 179 179 Important for enzyme activity (By
FT similarity).
FT MOD_RES 158 158 N6-acetyllysine.
FT VAR_SEQ 246 246 Missing (in isoform 2, isoform 3 and
FT isoform 4).
FT /FTId=VSP_005253.
FT VAR_SEQ 316 329 AKEKQNAKKAQETK -> GK (in isoform 2).
FT /FTId=VSP_005254.
FT VAR_SEQ 316 329 AKEKQNAKKAQETK -> FEKHFEKTLLGK (in
FT isoform 4).
FT /FTId=VSP_017062.
FT VARIANT 197 197 I -> F.
FT /FTId=VAR_011613.
FT MUTAGEN 88 88 C->A: Abolishes enzymatic activity.
FT CONFLICT 6 6 G -> V (in Ref. 2; AAD34065).
FT HELIX 15 24
FT STRAND 28 34
FT TURN 40 46
FT STRAND 48 56
FT STRAND 65 68
FT HELIX 72 75
FT HELIX 85 87
FT HELIX 88 98
FT HELIX 109 118
FT HELIX 123 131
FT HELIX 134 142
FT HELIX 159 162
FT STRAND 163 171
FT STRAND 174 178
FT STRAND 182 184
FT STRAND 186 190
FT STRAND 193 195
FT HELIX 197 213
FT STRAND 218 225
FT HELIX 227 236
FT HELIX 257 288
FT HELIX 293 300
FT HELIX 301 303
FT STRAND 304 306
FT TURN 307 311
SQ SEQUENCE 329 AA; 37607 MW; DF307347D48C9D0F CRC64;
MTGNAGEWCL MESDPGVFTE LIKGFGCRGA QVEEIWSLEP ENFEKLKPVH GLIFLFKWQP
GEEPAGSVVQ DSRLDTIFFA KQVINNACAT QAIVSVLLNC THQDVHLGET LSEFKEFSQS
FDAAMKGLAL SNSDVIRQVH NSFARQQMFE FDTKTSAKEE DAFHFVSYVP VNGRLYELDG
LREGPIDLGA CNQDDWISAV RPVIEKRIQK YSEGEIRFNL MAIVSDRKMI YEQKIAELQR
QLAEEEPMDT DQGNSMLSAI QSEVAKNQML IEEEVQKLKR YKIENIRRKH NYLPFIMELL
KTLAEHQQLI PLVEKAKEKQ NAKKAQETK
//
ID UCHL5_HUMAN Reviewed; 329 AA.
AC Q9Y5K5; Q5LJA6; Q5LJA7; Q8TBS4; Q96BJ9; Q9H1W5; Q9P0I3; Q9UQN2;
read moreDT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 3.
DT 22-JAN-2014, entry version 120.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase isozyme L5;
DE Short=UCH-L5;
DE EC=3.4.19.12;
DE AltName: Full=Ubiquitin C-terminal hydrolase UCH37;
DE AltName: Full=Ubiquitin thioesterase L5;
GN Name=UCHL5; Synonyms=UCH37; ORFNames=AD-019, CGI-70;
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), FUNCTION, ENZYME REGULATION,
RP MUTAGENESIS OF CYS-88, AND INTERACTION WITH ADRM1.
RX PubMed=16906146; DOI=10.1038/ncb1460;
RA Yao T., Song L., Xu W., DeMartino G.N., Florens L., Swanson S.K.,
RA Washburn M.P., Conaway R.C., Conaway J.W., Cohen R.E.;
RT "Proteasome recruitment and activation of the Uch37 deubiquitinating
RT enzyme by Adrm1.";
RL Nat. Cell Biol. 8:994-1002(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT
RP PHE-197.
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT
RP PHE-197.
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Lung, and Uterus;
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 [7]
RP INTERACTION WITH ADRM1, AND MASS SPECTROMETRY.
RX PubMed=16990800; DOI=10.1038/sj.emboj.7601338;
RA Hamazaki J., Iemura S., Natsume T., Yashiroda H., Tanaka K.,
RA Murata S.;
RT "A novel proteasome-interacting protein recruits the deubiquitinating
RT enzyme UCH37 to 26S proteasomes.";
RL EMBO J. 25:4524-4536(2006).
RN [8]
RP INTERACTION WITH ADRM1, ENZYME REGULATION, AND MASS SPECTROMETRY.
RX PubMed=17139257; DOI=10.1038/sj.emboj.7601450;
RA Qiu X.-B., Ouyang S.-Y., Li C.-J., Miao S., Wang L., Goldberg A.L.;
RT "hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds the
RT deubiquitinating enzyme, UCH37.";
RL EMBO J. 25:5742-5753(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17323924; DOI=10.1021/bi061994u;
RA Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L.;
RT "Mass spectrometric characterization of the affinity-purified human
RT 26S proteasome complex.";
RL Biochemistry 46:3553-3565(2007).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, IDENTIFICATION IN THE INO80
RP COMPLEX, INTERACTION WITH NFRKB AND ADRM1, AND ENZYME REGULATION.
RX PubMed=18922472; DOI=10.1016/j.molcel.2008.08.027;
RA Yao T., Song L., Jin J., Cai Y., Takahashi H., Swanson S.K.,
RA Washburn M.P., Florens L., Conaway R.C., Cohen R.E., Conaway J.W.;
RT "Distinct modes of regulation of the Uch37 deubiquitinating enzyme in
RT the proteasome and in the Ino80 chromatin-remodeling complex.";
RL Mol. Cell 31:909-917(2008).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-158, 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 [12]
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 [13]
RP IDENTIFICATION IN THE INO80 COMPLEX.
RX PubMed=21303910; DOI=10.1074/jbc.M111.222505;
RA Chen L., Cai Y., Jin J., Florens L., Swanson S.K., Washburn M.P.,
RA Conaway J.W., Conaway R.C.;
RT "Subunit organization of the human INO80 chromatin remodeling complex:
RT An evolutionarily conserved core complex catalyzes ATP-dependent
RT nucleosome remodeling.";
RL J. Biol. Chem. 286:11283-11289(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-228.
RX PubMed=19836345; DOI=10.1016/j.bbrc.2009.10.062;
RA Nishio K., Kim S.W., Kawai K., Mizushima T., Yamane T., Hamazaki J.,
RA Murata S., Tanaka K., Morimoto Y.;
RT "Crystal structure of the de-ubiquitinating enzyme UCH37 (human UCH-
RT L5) catalytic domain.";
RL Biochem. Biophys. Res. Commun. 390:855-860(2009).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 2-328.
RG Center for eukaryotic structural genomics (CESG);
RT "Crystal structure of UCH37.";
RL Submitted (AUG-2009) to the PDB data bank.
CC -!- FUNCTION: Protease that specifically cleaves 'Lys-48'-linked
CC polyubiquitin chains. Deubiquitinating enzyme associated with the
CC 19S regulatory subunit of the 26S proteasome. Putative regulatory
CC component of the INO80 complex; however is inactive in the INO80
CC complex and is activated by a transient interaction of the INO80
CC complex with the proteasome via ADRM1.
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 -!- ENZYME REGULATION: Activated by ADRM1. Inhibited by interaction
CC with NFRKB.
CC -!- SUBUNIT: Component of the 19S (PA700) regulatory complex of the
CC 26S proteasome. Interacts with ADRM1 and NFRKB; in vitro ADRM1 and
CC NFRKB compete for interaction with UCHL5. Component of the INO80
CC complex; specifically part of a complex module associated with N-
CC terminus of INO80.
CC -!- INTERACTION:
CC Q9H981:ACTR8; NbExp=3; IntAct=EBI-1051183, EBI-769597;
CC Q16186:ADRM1; NbExp=17; IntAct=EBI-1051183, EBI-954387;
CC Q8NBZ0:INO80E; NbExp=7; IntAct=EBI-1051183, EBI-769401;
CC Q6P4R8:NFRKB; NbExp=9; IntAct=EBI-1051183, EBI-2511210;
CC P60900:PSMA6; NbExp=4; IntAct=EBI-1051183, EBI-357793;
CC Q13200:PSMD2; NbExp=5; IntAct=EBI-1051183, EBI-357648;
CC P55036:PSMD4; NbExp=5; IntAct=EBI-1051183, EBI-359318;
CC P0C1Z6:TFPT; NbExp=3; IntAct=EBI-1051183, EBI-1245626;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Associates with the
CC proteasome 19S subunit in the cytoplasm. Associates with the INO80
CC complex in the nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Experimental confirmation may be lacking for some
CC isoforms;
CC Name=1;
CC IsoId=Q9Y5K5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y5K5-2; Sequence=VSP_005253, VSP_005254;
CC Name=3;
CC IsoId=Q9Y5K5-3; Sequence=VSP_005253;
CC Name=4;
CC IsoId=Q9Y5K5-4; Sequence=VSP_005253, VSP_017062;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the peptidase C12 family.
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DR EMBL; AF147717; AAD31528.1; -; mRNA.
DR EMBL; AF151828; AAD34065.1; -; mRNA.
DR EMBL; AF157320; AAF67486.1; -; mRNA.
DR EMBL; BT006790; AAP35436.1; -; mRNA.
DR EMBL; AL136370; CAI10829.1; -; Genomic_DNA.
DR EMBL; AL136370; CAI10830.1; -; Genomic_DNA.
DR EMBL; AL136370; CAI10831.1; -; Genomic_DNA.
DR EMBL; AL136370; CAI10833.1; -; Genomic_DNA.
DR EMBL; BC015521; AAH15521.1; -; mRNA.
DR EMBL; BC025369; AAH25369.1; -; mRNA.
DR RefSeq; NP_001186190.1; NM_001199261.1.
DR RefSeq; NP_001186191.1; NM_001199262.1.
DR RefSeq; NP_001186192.1; NM_001199263.1.
DR RefSeq; NP_057068.1; NM_015984.3.
DR UniGene; Hs.145469; -.
DR PDB; 3A7S; X-ray; 2.20 A; A=1-228.
DR PDB; 3IHR; X-ray; 2.95 A; A=2-329.
DR PDB; 3RII; X-ray; 2.00 A; A/B=1-228.
DR PDB; 3RIS; X-ray; 2.40 A; A/B/C/D=1-240.
DR PDB; 3TB3; X-ray; 2.30 A; A/B=1-227.
DR PDBsum; 3A7S; -.
DR PDBsum; 3IHR; -.
DR PDBsum; 3RII; -.
DR PDBsum; 3RIS; -.
DR PDBsum; 3TB3; -.
DR ProteinModelPortal; Q9Y5K5; -.
DR SMR; Q9Y5K5; 7-312.
DR DIP; DIP-42671N; -.
DR IntAct; Q9Y5K5; 58.
DR MINT; MINT-2823912; -.
DR STRING; 9606.ENSP00000356425; -.
DR MEROPS; C12.005; -.
DR PhosphoSite; Q9Y5K5; -.
DR DMDM; 108936023; -.
DR PaxDb; Q9Y5K5; -.
DR PRIDE; Q9Y5K5; -.
DR DNASU; 51377; -.
DR Ensembl; ENST00000367448; ENSP00000356418; ENSG00000116750.
DR Ensembl; ENST00000367449; ENSP00000356419; ENSG00000116750.
DR Ensembl; ENST00000367454; ENSP00000356424; ENSG00000116750.
DR Ensembl; ENST00000367455; ENSP00000356425; ENSG00000116750.
DR GeneID; 51377; -.
DR KEGG; hsa:51377; -.
DR UCSC; uc001gsm.3; human.
DR CTD; 51377; -.
DR GeneCards; GC01M192984; -.
DR HGNC; HGNC:19678; UCHL5.
DR HPA; HPA005908; -.
DR MIM; 610667; gene.
DR neXtProt; NX_Q9Y5K5; -.
DR PharmGKB; PA134916228; -.
DR eggNOG; NOG321645; -.
DR HOVERGEN; HBG056021; -.
DR KO; K05610; -.
DR PhylomeDB; Q9Y5K5; -.
DR BRENDA; 3.4.19.12; 2681.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR SignaLink; Q9Y5K5; -.
DR ChiTaRS; UCHL5; human.
DR EvolutionaryTrace; Q9Y5K5; -.
DR GeneWiki; Ubiquitin_carboxyl-terminal_hydrolase_L5; -.
DR GenomeRNAi; 51377; -.
DR NextBio; 54875; -.
DR PRO; PR:Q9Y5K5; -.
DR ArrayExpress; Q9Y5K5; -.
DR Bgee; Q9Y5K5; -.
DR CleanEx; HS_UCHL5; -.
DR Genevestigator; Q9Y5K5; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031011; C:Ino80 complex; IDA:UniProtKB.
DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW.
DR GO; GO:0004843; F:deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IMP:UniProtKB.
DR GO; GO:0008242; F:omega peptidase activity; IEA:InterPro.
DR GO; GO:0070628; F:proteasome binding; IDA:UniProtKB.
DR GO; GO:0004221; F:ubiquitin thiolesterase activity; IEA:InterPro.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0048853; P:forebrain morphogenesis; IEA:Ensembl.
DR GO; GO:0021670; P:lateral ventricle development; IEA:Ensembl.
DR GO; GO:0030901; P:midbrain development; IEA:Ensembl.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:Reactome.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.40.532.10; -; 1.
DR InterPro; IPR001578; Peptidase_C12.
DR InterPro; IPR017390; Ubiquitinyl_hydrolase_UCH37.
DR PANTHER; PTHR10589; PTHR10589; 1.
DR Pfam; PF01088; Peptidase_C12; 1.
DR PIRSF; PIRSF038120; Ubiquitinyl_hydrolase_UCH37; 1.
DR PRINTS; PR00707; UBCTHYDRLASE.
DR PROSITE; PS00140; UCH_1; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; DNA damage; DNA recombination; DNA repair; Hydrolase;
KW Nucleus; Polymorphism; Protease; Proteasome; Reference proteome;
KW Thiol protease; Transcription; Transcription regulation;
KW Ubl conjugation pathway.
FT CHAIN 1 329 Ubiquitin carboxyl-terminal hydrolase
FT isozyme L5.
FT /FTId=PRO_0000211066.
FT REGION 313 329 Interaction with ADRM1.
FT ACT_SITE 88 88 Nucleophile (Probable).
FT ACT_SITE 164 164 Proton donor (By similarity).
FT SITE 179 179 Important for enzyme activity (By
FT similarity).
FT MOD_RES 158 158 N6-acetyllysine.
FT VAR_SEQ 246 246 Missing (in isoform 2, isoform 3 and
FT isoform 4).
FT /FTId=VSP_005253.
FT VAR_SEQ 316 329 AKEKQNAKKAQETK -> GK (in isoform 2).
FT /FTId=VSP_005254.
FT VAR_SEQ 316 329 AKEKQNAKKAQETK -> FEKHFEKTLLGK (in
FT isoform 4).
FT /FTId=VSP_017062.
FT VARIANT 197 197 I -> F.
FT /FTId=VAR_011613.
FT MUTAGEN 88 88 C->A: Abolishes enzymatic activity.
FT CONFLICT 6 6 G -> V (in Ref. 2; AAD34065).
FT HELIX 15 24
FT STRAND 28 34
FT TURN 40 46
FT STRAND 48 56
FT STRAND 65 68
FT HELIX 72 75
FT HELIX 85 87
FT HELIX 88 98
FT HELIX 109 118
FT HELIX 123 131
FT HELIX 134 142
FT HELIX 159 162
FT STRAND 163 171
FT STRAND 174 178
FT STRAND 182 184
FT STRAND 186 190
FT STRAND 193 195
FT HELIX 197 213
FT STRAND 218 225
FT HELIX 227 236
FT HELIX 257 288
FT HELIX 293 300
FT HELIX 301 303
FT STRAND 304 306
FT TURN 307 311
SQ SEQUENCE 329 AA; 37607 MW; DF307347D48C9D0F CRC64;
MTGNAGEWCL MESDPGVFTE LIKGFGCRGA QVEEIWSLEP ENFEKLKPVH GLIFLFKWQP
GEEPAGSVVQ DSRLDTIFFA KQVINNACAT QAIVSVLLNC THQDVHLGET LSEFKEFSQS
FDAAMKGLAL SNSDVIRQVH NSFARQQMFE FDTKTSAKEE DAFHFVSYVP VNGRLYELDG
LREGPIDLGA CNQDDWISAV RPVIEKRIQK YSEGEIRFNL MAIVSDRKMI YEQKIAELQR
QLAEEEPMDT DQGNSMLSAI QSEVAKNQML IEEEVQKLKR YKIENIRRKH NYLPFIMELL
KTLAEHQQLI PLVEKAKEKQ NAKKAQETK
//
MIM
610667
*RECORD*
*FIELD* NO
610667
*FIELD* TI
*610667 UBIQUITIN CARBOXYL-TERMINAL HYDROLASE L5; UCHL5
;;UCH37
*FIELD* TX
CLONING
read more
Using yeast 2-hybrid analysis of a mouse brain library with the
N-terminal region of Smad3 (603109) as bait, Wicks et al. (2005)
identified mouse Uchl5. They stated that mouse Uchl5 and human UCH37
(UCHL5) are 99% identical. UCHL5 is a member of the UCH enzyme family
and contains a conserved catalytic domain and a nonconserved extended
C-terminal tail.
GENE FUNCTION
Lam et al. (1997, 1997) originally identified bovine UCHL5 as a
component of the 26S proteasome and showed that it functions in editing
polyubiquitinated protein substrates.
Wicks et al. (2005) reported that proteasome-associated UCHL5
sequentially removes ubiquitin from the distal end of the lys48-linked
polyubiquitin chain and has the potential to rescue ubiquitinated
substrates from proteasomal degradation. Using a variety of
immunoprecipitation assays, they found that mouse Uchl5 binds strongly
to Smad7 (602932) and weakly to Smad2 (601366) and Smad3. Deletion
constructs showed that Uchl5 binding does not require the Smurf-binding
PY motif of Smad7. Transfection experiments with transforming growth
factor-beta receptor-1 (Tgfbr1; 190181), Smad7, Smurf2 (605532), and
Uchl5 showed that Uchl5 deubiquitinates and stabilizes TGFBR1. Using a
luciferase reporter construct in HEK-293 cells, Wicks et al. (2005)
showed that Uchl5 overexpression increases Tgfbr1-dependent
transcription. Knockdown of Uchl5 expression by RNA interference
abrogated Tgf-beta-dependent transcription.
Rolen et al. (2006) reported that deregulation of some
ubiquitin-specific proteases (USPs) affect tumor growth. Using a
functional proteomics assay in which tagged probes target the active
sites of USPs, they investigated the activity of USPs in human
HPV-carrying cervical carcinoma biopsies relative to adjacent normal
tissue. The activity of UCHL5 was significantly increased in 76% of the
tumors analyzed. UCHL5 was active in 92% (24 of 26) of the cervical
carcinoma biopsies, and in 100% of 8 cervical carcinoma cell lines, of
which 6 were HPV-positive and 2 were HPV-negative. UCHL5 activity level
did not correlate with the clinical stage of the tumors or the presence
of metastases.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the UCHL5
gene to chromosome 1 (TMAP WI-14924).
*FIELD* RF
1. Lam, Y. A.; DeMartino, G. N.; Pickart, C. M.; Cohen, R. E.: Specificity
of the ubiquitin isopeptidase in the PA700 regulatory complex of 26S
proteasomes. J. Biol. Chem. 272: 28438-28446, 1997.
2. Lam, Y. A.; Xu, W.; DeMartino, G. N.; Cohen, R. E.: Editing of
ubiquitin conjugates by an isopeptidase in the 26S proteasome. Nature 385:
737-740, 1997.
3. Rolen, U.; Kobzeva, V.; Gasparjan, N.; Ovaa, H.; Winberg, G.; Kisseljov,
F.; Masucci, M. G.: Activity profiling of deubiquitinating enzymes
in cervical carcinoma biopsies and cell lines. Molec. Carcinogen. 45:
260-269, 2006.
4. Wicks, S. J.; Haros, K.; Maillard, M.; Song, L.; Cohen, R. E.;
ten Dijke, P.; Chantry, A.: The deubiquitinating enzyme UCH37 interacts
with Smads and regulates TGF-beta signalling. Oncogene 24: 8080-8084,
2005.
*FIELD* CD
Laura L. Baxter: 12/20/2006
*FIELD* ED
carol: 12/26/2007
carol: 12/21/2006
*RECORD*
*FIELD* NO
610667
*FIELD* TI
*610667 UBIQUITIN CARBOXYL-TERMINAL HYDROLASE L5; UCHL5
;;UCH37
*FIELD* TX
CLONING
read more
Using yeast 2-hybrid analysis of a mouse brain library with the
N-terminal region of Smad3 (603109) as bait, Wicks et al. (2005)
identified mouse Uchl5. They stated that mouse Uchl5 and human UCH37
(UCHL5) are 99% identical. UCHL5 is a member of the UCH enzyme family
and contains a conserved catalytic domain and a nonconserved extended
C-terminal tail.
GENE FUNCTION
Lam et al. (1997, 1997) originally identified bovine UCHL5 as a
component of the 26S proteasome and showed that it functions in editing
polyubiquitinated protein substrates.
Wicks et al. (2005) reported that proteasome-associated UCHL5
sequentially removes ubiquitin from the distal end of the lys48-linked
polyubiquitin chain and has the potential to rescue ubiquitinated
substrates from proteasomal degradation. Using a variety of
immunoprecipitation assays, they found that mouse Uchl5 binds strongly
to Smad7 (602932) and weakly to Smad2 (601366) and Smad3. Deletion
constructs showed that Uchl5 binding does not require the Smurf-binding
PY motif of Smad7. Transfection experiments with transforming growth
factor-beta receptor-1 (Tgfbr1; 190181), Smad7, Smurf2 (605532), and
Uchl5 showed that Uchl5 deubiquitinates and stabilizes TGFBR1. Using a
luciferase reporter construct in HEK-293 cells, Wicks et al. (2005)
showed that Uchl5 overexpression increases Tgfbr1-dependent
transcription. Knockdown of Uchl5 expression by RNA interference
abrogated Tgf-beta-dependent transcription.
Rolen et al. (2006) reported that deregulation of some
ubiquitin-specific proteases (USPs) affect tumor growth. Using a
functional proteomics assay in which tagged probes target the active
sites of USPs, they investigated the activity of USPs in human
HPV-carrying cervical carcinoma biopsies relative to adjacent normal
tissue. The activity of UCHL5 was significantly increased in 76% of the
tumors analyzed. UCHL5 was active in 92% (24 of 26) of the cervical
carcinoma biopsies, and in 100% of 8 cervical carcinoma cell lines, of
which 6 were HPV-positive and 2 were HPV-negative. UCHL5 activity level
did not correlate with the clinical stage of the tumors or the presence
of metastases.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the UCHL5
gene to chromosome 1 (TMAP WI-14924).
*FIELD* RF
1. Lam, Y. A.; DeMartino, G. N.; Pickart, C. M.; Cohen, R. E.: Specificity
of the ubiquitin isopeptidase in the PA700 regulatory complex of 26S
proteasomes. J. Biol. Chem. 272: 28438-28446, 1997.
2. Lam, Y. A.; Xu, W.; DeMartino, G. N.; Cohen, R. E.: Editing of
ubiquitin conjugates by an isopeptidase in the 26S proteasome. Nature 385:
737-740, 1997.
3. Rolen, U.; Kobzeva, V.; Gasparjan, N.; Ovaa, H.; Winberg, G.; Kisseljov,
F.; Masucci, M. G.: Activity profiling of deubiquitinating enzymes
in cervical carcinoma biopsies and cell lines. Molec. Carcinogen. 45:
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*FIELD* CD
Laura L. Baxter: 12/20/2006
*FIELD* ED
carol: 12/26/2007
carol: 12/21/2006