Full text data of USP5
USP5
(ISOT)
[Confidence: high (present in two of the MS resources)]
Ubiquitin carboxyl-terminal hydrolase 5; 3.4.19.12 (Deubiquitinating enzyme 5; Isopeptidase T; Ubiquitin thioesterase 5; Ubiquitin-specific-processing protease 5)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ubiquitin carboxyl-terminal hydrolase 5; 3.4.19.12 (Deubiquitinating enzyme 5; Isopeptidase T; Ubiquitin thioesterase 5; Ubiquitin-specific-processing protease 5)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00024664
IPI00024664 Splice Isoform 1 Of Ubiquitin carboxyl-terminal hydrolase 5 Cleaves linear and branched multiubiquitin polymers with a marked preference for branched polymers. 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 Isoform 1 or 2 found at its expected molecular weight found at molecular weight
IPI00024664 Splice Isoform 1 Of Ubiquitin carboxyl-terminal hydrolase 5 Cleaves linear and branched multiubiquitin polymers with a marked preference for branched polymers. 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 Isoform 1 or 2 found at its expected molecular weight found at molecular weight
UniProt
P45974
ID UBP5_HUMAN Reviewed; 858 AA.
AC P45974; D3DUS7; D3DUS8; Q96J22;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 2.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 5;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 5;
DE AltName: Full=Isopeptidase T;
DE AltName: Full=Ubiquitin thioesterase 5;
DE AltName: Full=Ubiquitin-specific-processing protease 5;
GN Name=USP5; Synonyms=ISOT;
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], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=7498549; DOI=10.1016/0014-5793(95)01287-7;
RA Falquet L., Paquet N., Frutiger S., Hughes G.J., Hoang-Van K.,
RA Jaton J.-C.;
RT "cDNA cloning of a human 100 kDa de-ubiquitinating enzyme: the 100 kDa
RT human de-ubiquitinase belongs to the ubiquitin C-terminal hydrolase
RT family 2 (UCH2).";
RL FEBS Lett. 376:233-237(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=8723724;
RA Ansari-Lari M.A., Muzny D.M., Lu J., Lu F., Lilley C.E., Spanos S.,
RA Malley T., Gibbs R.A.;
RT "A gene-rich cluster between the CD4 and triosephosphate isomerase
RT genes at human chromosome 12p13.";
RL Genome Res. 6:314-326(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9074930;
RA Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A.;
RT "Large-scale sequencing in human chromosome 12p13: experimental and
RT computational gene structure determination.";
RL Genome Res. 7:268-280(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Tashayev V.L., O'Connor L.B., Larsen C.N., Kasperek E., Pickart C.M.;
RL Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG AND SHORT).
RC TISSUE=Kidney, and Lung;
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 CHARACTERIZATION.
RX PubMed=7851534; DOI=10.1016/0014-5793(94)01451-6;
RA Falquet L., Paquet N., Frutiger S., Hughes G.J., Hoang-Van K.,
RA Jaton J.-C.;
RT "A human de-ubiquitinating enzyme with both isopeptidase and peptidase
RT activities in vitro.";
RL FEBS Lett. 359:73-77(1995).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [9]
RP MUTAGENESIS OF ARG-221; CYS-335; ASP-435; MET-666 AND MET-734, AND
RP POLYUBIQUITIN BINDING.
RX PubMed=18482987; DOI=10.1074/jbc.M800947200;
RA Reyes-Turcu F.E., Shanks J.R., Komander D., Wilkinson K.D.;
RT "Recognition of polyubiquitin isoforms by the multiple ubiquitin
RT binding modules of isopeptidase T.";
RL J. Biol. Chem. 283:19581-19592(2008).
RN [10]
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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP FUNCTION.
RX PubMed=19098288; DOI=10.1074/jbc.M805871200;
RA Dayal S., Sparks A., Jacob J., Allende-Vega N., Lane D.P.,
RA Saville M.K.;
RT "Suppression of the deubiquitinating enzyme USP5 causes the
RT accumulation of unanchored polyubiquitin and the activation of p53.";
RL J. Biol. Chem. 284:5030-5041(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-783, 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-783, AND MASS
RP 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 MUTAGENESIS OF 221-ARG--TYR-223 AND TYR-261.
RX PubMed=22216260; DOI=10.1371/journal.pone.0029362;
RA Zhang Y.H., Zhou C.J., Zhou Z.R., Song A.X., Hu H.Y.;
RT "Domain analysis reveals that a deubiquitinating enzyme USP13 performs
RT non-activating catalysis for Lys63-linked polyubiquitin.";
RL PLoS ONE 6:E29362-E29362(2011).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) OF 163-291 IN COMPLEX WITH
RP UBIQUITIN, ZINC-BINDING, AND MUTAGENESIS OF CYS-199; CYS-202; CYS-219
RP AND HIS-232.
RX PubMed=16564012; DOI=10.1016/j.cell.2006.02.038;
RA Reyes-Turcu F.E., Horton J.R., Mullally J.E., Heroux A., Cheng X.,
RA Wilkinson K.D.;
RT "The ubiquitin binding domain ZnF UBP recognizes the C-terminal
RT diglycine motif of unanchored ubiquitin.";
RL Cell 124:1197-1208(2006).
RN [19]
RP STRUCTURE BY NMR OF 655-772.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the first and second UBA domains in the human
RT ubiquitin specific protease 5 (isopeptidase 5).";
RL Submitted (JUN-2006) to the PDB data bank.
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-858 IN COMPLEX WITH
RP UBIQUITIN, DISULFIDE BOND, AND ZINC-BINDING.
RA Walker J.R., Avvakumov G.V., Xue S., Butler-Cole C., Weigelt J.,
RA Bountra C., Arrowsmith C.H., Edwards A.M., Bochkarev A.,
RA Dhe-Paganon S.;
RT "Covalent ubiquitin-USP5 complex.";
RL Submitted (DEC-2009) to the PDB data bank.
CC -!- FUNCTION: Cleaves linear and branched multiubiquitin polymers with
CC a marked preference for branched polymers. Involved in unanchored
CC 'Lys-48'-linked polyubiquitin disassembly. Binds linear and 'Lys-
CC 63'-linked polyubiquitin with a lower affinity. Knock-down of USP5
CC causes the accumulation of p53/TP53 and an increase in p53/TP53
CC transcriptional activity because the unanchored polyubiquitin that
CC accumulates is able to compete with ubiquitinated p53/TP53 but not
CC with MDM2 for proteasomal recognition.
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 -!- COFACTOR: Binds 1 zinc ion.
CC -!- SUBUNIT: Interacts with TRIML1 (By similarity).
CC -!- INTERACTION:
CC P54727:RAD23B; NbExp=2; IntAct=EBI-741277, EBI-954531;
CC O75528:TADA3; NbExp=2; IntAct=EBI-741277, EBI-473249;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P45974-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P45974-2; Sequence=VSP_005259;
CC -!- DOMAIN: The UBP-type zinc finger domain interacts selectively with
CC an unmodified C-terminus of the proximal ubiquitin. Both UBA
CC domains are involved in polyubiquitin recognition.
CC -!- MISCELLANEOUS: The UBP-type zinc finger domain crystallizes as a
CC dimer linked by a disulfide bond between the Cys-195 residues of
CC both molecules, but there is no evidence that the full-length USP5
CC exists as a dimer.
CC -!- SIMILARITY: Belongs to the peptidase C19 family.
CC -!- SIMILARITY: Contains 2 UBA domains.
CC -!- SIMILARITY: Contains 1 UBP-type zinc finger.
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DR EMBL; X91349; CAA62690.1; -; mRNA.
DR EMBL; U47927; AAC50465.1; -; mRNA.
DR EMBL; U47924; AAB51314.1; -; Genomic_DNA.
DR EMBL; U47924; AAB51315.1; -; Genomic_DNA.
DR EMBL; U35116; AAA78934.1; -; mRNA.
DR EMBL; CH471116; EAW88724.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88725.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88726.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88727.1; -; Genomic_DNA.
DR EMBL; BC004889; AAH04889.1; -; mRNA.
DR EMBL; BC005139; AAH05139.1; -; mRNA.
DR PIR; S68227; S68227.
DR RefSeq; NP_001092006.1; NM_001098536.1.
DR RefSeq; NP_003472.2; NM_003481.2.
DR UniGene; Hs.631661; -.
DR PDB; 2DAG; NMR; -; A=655-715.
DR PDB; 2DAK; NMR; -; A=723-772.
DR PDB; 2G43; X-ray; 2.09 A; A/B=163-291.
DR PDB; 2G45; X-ray; 1.99 A; A/D=163-291.
DR PDB; 3IHP; X-ray; 2.80 A; A/B=1-858.
DR PDBsum; 2DAG; -.
DR PDBsum; 2DAK; -.
DR PDBsum; 2G43; -.
DR PDBsum; 2G45; -.
DR PDBsum; 3IHP; -.
DR ProteinModelPortal; P45974; -.
DR SMR; P45974; 1-858.
DR IntAct; P45974; 7.
DR MINT; MINT-5001006; -.
DR STRING; 9606.ENSP00000229268; -.
DR ChEMBL; CHEMBL6158; -.
DR MEROPS; C19.001; -.
DR PhosphoSite; P45974; -.
DR DMDM; 1717869; -.
DR REPRODUCTION-2DPAGE; IPI00375145; -.
DR PaxDb; P45974; -.
DR PRIDE; P45974; -.
DR DNASU; 8078; -.
DR Ensembl; ENST00000229268; ENSP00000229268; ENSG00000111667.
DR Ensembl; ENST00000389231; ENSP00000373883; ENSG00000111667.
DR Ensembl; ENST00000595281; ENSP00000472079; ENSG00000268462.
DR Ensembl; ENST00000597018; ENSP00000470388; ENSG00000268462.
DR GeneID; 8078; -.
DR KEGG; hsa:8078; -.
DR UCSC; uc001qri.4; human.
DR CTD; 8078; -.
DR GeneCards; GC12P007111; -.
DR HGNC; HGNC:12628; USP5.
DR HPA; HPA006756; -.
DR MIM; 601447; gene.
DR neXtProt; NX_P45974; -.
DR PharmGKB; PA37253; -.
DR eggNOG; COG5207; -.
DR HOGENOM; HOG000162311; -.
DR HOVERGEN; HBG002833; -.
DR InParanoid; P45974; -.
DR KO; K11836; -.
DR OMA; LRWEFSM; -.
DR PhylomeDB; P45974; -.
DR ChiTaRS; USP5; human.
DR EvolutionaryTrace; P45974; -.
DR GeneWiki; USP5; -.
DR GenomeRNAi; 8078; -.
DR NextBio; 30687; -.
DR PMAP-CutDB; P45974; -.
DR PRO; PR:P45974; -.
DR ArrayExpress; P45974; -.
DR Bgee; P45974; -.
DR CleanEx; HS_USP5; -.
DR Genevestigator; P45974; -.
DR GO; GO:0005764; C:lysosome; TAS:ProtInc.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0008242; F:omega peptidase activity; IEA:InterPro.
DR GO; GO:0004221; F:ubiquitin thiolesterase activity; TAS:ProtInc.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR018200; Pept_C19ubi-hydrolase_C_CS.
DR InterPro; IPR001394; Peptidase_C19/C67.
DR InterPro; IPR009060; UBA-like.
DR InterPro; IPR015940; UBA/transl_elong_EF1B_N_euk.
DR InterPro; IPR000449; UBA/Ts_N.
DR InterPro; IPR016652; Ubiquitinyl_hydrolase.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001607; Znf_UBP.
DR Pfam; PF00627; UBA; 2.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF02148; zf-UBP; 1.
DR PIRSF; PIRSF016308; UBP; 1.
DR SMART; SM00165; UBA; 2.
DR SMART; SM00290; ZnF_UBP; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR PROSITE; PS50030; UBA; 2.
DR PROSITE; PS00972; UCH_2_1; 1.
DR PROSITE; PS00973; UCH_2_2; 1.
DR PROSITE; PS50235; UCH_2_3; 1.
DR PROSITE; PS50271; ZF_UBP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Hydrolase; Metal-binding;
KW Phosphoprotein; Protease; Reference proteome; Repeat; Thiol protease;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 858 Ubiquitin carboxyl-terminal hydrolase 5.
FT /FTId=PRO_0000080623.
FT DOMAIN 654 695 UBA 1.
FT DOMAIN 722 762 UBA 2.
FT ZN_FING 197 269 UBP-type.
FT REGION 221 224 Substrate binding.
FT ACT_SITE 335 335 Nucleophile.
FT ACT_SITE 818 818 Proton acceptor (By similarity).
FT METAL 199 199 Zinc.
FT METAL 202 202 Zinc.
FT METAL 219 219 Zinc.
FT METAL 232 232 Zinc.
FT BINDING 209 209 Substrate.
FT BINDING 259 259 Substrate.
FT BINDING 261 261 Substrate; via carbonyl oxygen.
FT BINDING 264 264 Substrate.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 623 623 Phosphothreonine (By similarity).
FT MOD_RES 783 783 Phosphoserine.
FT DISULFID 195 816
FT VAR_SEQ 629 652 GSLGFYGNEDEDSFCSPHFSSPTS -> A (in isoform
FT Short).
FT /FTId=VSP_005259.
FT MUTAGEN 199 199 C->A: Decreased rate of activity and
FT decreased zinc binding.
FT MUTAGEN 202 202 C->A: Decreased rate of activity.
FT MUTAGEN 219 219 C->A: Decreased rate of activity.
FT MUTAGEN 221 223 RRY->KWF: Loss of polyubiquitin binding
FT and subsequent activation.
FT MUTAGEN 221 221 R->A: Loss of polyubiquitin hydrolysis.
FT Loss of ubiquitin binding; when
FT associated with A-335.
FT MUTAGEN 232 232 H->A: Decreased rate of activity.
FT MUTAGEN 261 261 Y->F: Loss of polyubiquitin binding.
FT MUTAGEN 335 335 C->A: Loss of activity. Loss of ubiquitin
FT binding; when associated with A-221.
FT Lower affinity for triubiquitin and
FT tetraubiquitin, but no effect on affinity
FT for diubiquitin; when associated with E-
FT 666. Lower affinity for diubiquitin,
FT triubiquitin and tetraubiquitin; when
FT associated with E-734.
FT MUTAGEN 435 435 D->A: Loss of polyubiquitin binding and
FT hydrolysis.
FT MUTAGEN 666 666 M->E: Lower affinity for triubiquitin and
FT tetraubiquitin, but no effect on affinity
FT for diubiquitin; when associated with A-
FT 335. No effect on activity; when
FT associated with E-734.
FT MUTAGEN 734 734 M->E: Lower affinity for diubiquitin,
FT triubiquitin and tetraubiquitin; when
FT associated with A-335. No effect on
FT activity; when associated with E-666.
FT CONFLICT 3 4 EL -> DV (in Ref. 1; CAA62690).
FT CONFLICT 45 45 I -> V (in Ref. 1; CAA62690).
FT CONFLICT 468 468 K -> R (in Ref. 4; AAA78934).
FT CONFLICT 681 681 G -> D (in Ref. 4; AAA78934).
FT HELIX 5 11
FT HELIX 12 15
FT STRAND 31 34
FT STRAND 43 46
FT TURN 47 49
FT TURN 55 57
FT HELIX 58 65
FT STRAND 69 75
FT STRAND 118 124
FT TURN 125 128
FT STRAND 129 131
FT HELIX 141 154
FT TURN 178 182
FT STRAND 200 203
FT STRAND 206 211
FT TURN 212 214
FT STRAND 217 219
FT HELIX 232 240
FT STRAND 244 247
FT STRAND 258 260
FT TURN 261 264
FT STRAND 265 268
FT HELIX 272 277
FT TURN 278 280
FT TURN 283 285
FT HELIX 335 344
FT HELIX 348 354
FT TURN 355 357
FT HELIX 358 364
FT HELIX 369 371
FT HELIX 373 385
FT HELIX 415 421
FT TURN 422 424
FT TURN 426 429
FT STRAND 430 432
FT HELIX 436 449
FT HELIX 457 460
FT STRAND 463 471
FT TURN 472 475
FT STRAND 476 489
FT HELIX 493 495
FT HELIX 499 514
FT HELIX 529 537
FT STRAND 540 547
FT TURN 548 551
FT STRAND 552 564
FT STRAND 567 573
FT STRAND 576 578
FT HELIX 580 582
FT STRAND 584 586
FT STRAND 595 598
FT HELIX 600 602
FT HELIX 658 666
FT HELIX 670 679
FT HELIX 685 695
FT HELIX 700 702
FT HELIX 725 732
FT TURN 733 735
FT HELIX 738 747
FT TURN 748 750
FT HELIX 752 770
FT STRAND 799 812
FT STRAND 818 825
FT STRAND 828 833
FT STRAND 836 839
FT STRAND 849 855
SQ SEQUENCE 858 AA; 95786 MW; E99CB7CDFA682C65 CRC64;
MAELSEEALL SVLPTIRVPK AGDRVHKDEC AFSFDTPESE GGLYICMNTF LGFGKQYVER
HFNKTGQRVY LHLRRTRRPK EEDPATGTGD PPRKKPTRLA IGVEGGFDLS EEKFELDEDV
KIVILPDYLE IARDGLGGLP DIVRDRVTSA VEALLSADSA SRKQEVQAWD GEVRQVSKHA
FSLKQLDNPA RIPPCGWKCS KCDMRENLWL NLTDGSILCG RRYFDGSGGN NHAVEHYRET
GYPLAVKLGT ITPDGADVYS YDEDDMVLDP SLAEHLSHFG IDMLKMQKTD KTMTELEIDM
NQRIGEWELI QESGVPLKPL FGPGYTGIRN LGNSCYLNSV VQVLFSIPDF QRKYVDKLEK
IFQNAPTDPT QDFSTQVAKL GHGLLSGEYS KPVPESGDGE RVPEQKEVQD GIAPRMFKAL
IGKGHPEFST NRQQDAQEFF LHLINMVERN CRSSENPNEV FRFLVEEKIK CLATEKVKYT
QRVDYIMQLP VPMDAALNKE ELLEYEEKKR QAEEEKMALP ELVRAQVPFS SCLEAYGAPE
QVDDFWSTAL QAKSVAVKTT RFASFPDYLV IQIKKFTFGL DWVPKKLDVS IEMPEELDIS
QLRGTGLQPG EEELPDIAPP LVTPDEPKGS LGFYGNEDED SFCSPHFSSP TSPMLDESVI
IQLVEMGFPM DACRKAVYYT GNSGAEAAMN WVMSHMDDPD FANPLILPGS SGPGSTSAAA
DPPPEDCVTT IVSMGFSRDQ ALKALRATNN SLERAVDWIF SHIDDLDAEA AMDISEGRSA
ADSISESVPV GPKVRDGPGK YQLFAFISHM GTSTMCGHYV CHIKKEGRWV IYNDQKVCAS
EKPPKDLGYI YFYQRVAS
//
ID UBP5_HUMAN Reviewed; 858 AA.
AC P45974; D3DUS7; D3DUS8; Q96J22;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 2.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 5;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 5;
DE AltName: Full=Isopeptidase T;
DE AltName: Full=Ubiquitin thioesterase 5;
DE AltName: Full=Ubiquitin-specific-processing protease 5;
GN Name=USP5; Synonyms=ISOT;
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], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=7498549; DOI=10.1016/0014-5793(95)01287-7;
RA Falquet L., Paquet N., Frutiger S., Hughes G.J., Hoang-Van K.,
RA Jaton J.-C.;
RT "cDNA cloning of a human 100 kDa de-ubiquitinating enzyme: the 100 kDa
RT human de-ubiquitinase belongs to the ubiquitin C-terminal hydrolase
RT family 2 (UCH2).";
RL FEBS Lett. 376:233-237(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=8723724;
RA Ansari-Lari M.A., Muzny D.M., Lu J., Lu F., Lilley C.E., Spanos S.,
RA Malley T., Gibbs R.A.;
RT "A gene-rich cluster between the CD4 and triosephosphate isomerase
RT genes at human chromosome 12p13.";
RL Genome Res. 6:314-326(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9074930;
RA Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A.;
RT "Large-scale sequencing in human chromosome 12p13: experimental and
RT computational gene structure determination.";
RL Genome Res. 7:268-280(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Tashayev V.L., O'Connor L.B., Larsen C.N., Kasperek E., Pickart C.M.;
RL Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG AND SHORT).
RC TISSUE=Kidney, and Lung;
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 CHARACTERIZATION.
RX PubMed=7851534; DOI=10.1016/0014-5793(94)01451-6;
RA Falquet L., Paquet N., Frutiger S., Hughes G.J., Hoang-Van K.,
RA Jaton J.-C.;
RT "A human de-ubiquitinating enzyme with both isopeptidase and peptidase
RT activities in vitro.";
RL FEBS Lett. 359:73-77(1995).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [9]
RP MUTAGENESIS OF ARG-221; CYS-335; ASP-435; MET-666 AND MET-734, AND
RP POLYUBIQUITIN BINDING.
RX PubMed=18482987; DOI=10.1074/jbc.M800947200;
RA Reyes-Turcu F.E., Shanks J.R., Komander D., Wilkinson K.D.;
RT "Recognition of polyubiquitin isoforms by the multiple ubiquitin
RT binding modules of isopeptidase T.";
RL J. Biol. Chem. 283:19581-19592(2008).
RN [10]
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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP FUNCTION.
RX PubMed=19098288; DOI=10.1074/jbc.M805871200;
RA Dayal S., Sparks A., Jacob J., Allende-Vega N., Lane D.P.,
RA Saville M.K.;
RT "Suppression of the deubiquitinating enzyme USP5 causes the
RT accumulation of unanchored polyubiquitin and the activation of p53.";
RL J. Biol. Chem. 284:5030-5041(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-783, 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-783, AND MASS
RP 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 MUTAGENESIS OF 221-ARG--TYR-223 AND TYR-261.
RX PubMed=22216260; DOI=10.1371/journal.pone.0029362;
RA Zhang Y.H., Zhou C.J., Zhou Z.R., Song A.X., Hu H.Y.;
RT "Domain analysis reveals that a deubiquitinating enzyme USP13 performs
RT non-activating catalysis for Lys63-linked polyubiquitin.";
RL PLoS ONE 6:E29362-E29362(2011).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) OF 163-291 IN COMPLEX WITH
RP UBIQUITIN, ZINC-BINDING, AND MUTAGENESIS OF CYS-199; CYS-202; CYS-219
RP AND HIS-232.
RX PubMed=16564012; DOI=10.1016/j.cell.2006.02.038;
RA Reyes-Turcu F.E., Horton J.R., Mullally J.E., Heroux A., Cheng X.,
RA Wilkinson K.D.;
RT "The ubiquitin binding domain ZnF UBP recognizes the C-terminal
RT diglycine motif of unanchored ubiquitin.";
RL Cell 124:1197-1208(2006).
RN [19]
RP STRUCTURE BY NMR OF 655-772.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the first and second UBA domains in the human
RT ubiquitin specific protease 5 (isopeptidase 5).";
RL Submitted (JUN-2006) to the PDB data bank.
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-858 IN COMPLEX WITH
RP UBIQUITIN, DISULFIDE BOND, AND ZINC-BINDING.
RA Walker J.R., Avvakumov G.V., Xue S., Butler-Cole C., Weigelt J.,
RA Bountra C., Arrowsmith C.H., Edwards A.M., Bochkarev A.,
RA Dhe-Paganon S.;
RT "Covalent ubiquitin-USP5 complex.";
RL Submitted (DEC-2009) to the PDB data bank.
CC -!- FUNCTION: Cleaves linear and branched multiubiquitin polymers with
CC a marked preference for branched polymers. Involved in unanchored
CC 'Lys-48'-linked polyubiquitin disassembly. Binds linear and 'Lys-
CC 63'-linked polyubiquitin with a lower affinity. Knock-down of USP5
CC causes the accumulation of p53/TP53 and an increase in p53/TP53
CC transcriptional activity because the unanchored polyubiquitin that
CC accumulates is able to compete with ubiquitinated p53/TP53 but not
CC with MDM2 for proteasomal recognition.
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 -!- COFACTOR: Binds 1 zinc ion.
CC -!- SUBUNIT: Interacts with TRIML1 (By similarity).
CC -!- INTERACTION:
CC P54727:RAD23B; NbExp=2; IntAct=EBI-741277, EBI-954531;
CC O75528:TADA3; NbExp=2; IntAct=EBI-741277, EBI-473249;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P45974-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P45974-2; Sequence=VSP_005259;
CC -!- DOMAIN: The UBP-type zinc finger domain interacts selectively with
CC an unmodified C-terminus of the proximal ubiquitin. Both UBA
CC domains are involved in polyubiquitin recognition.
CC -!- MISCELLANEOUS: The UBP-type zinc finger domain crystallizes as a
CC dimer linked by a disulfide bond between the Cys-195 residues of
CC both molecules, but there is no evidence that the full-length USP5
CC exists as a dimer.
CC -!- SIMILARITY: Belongs to the peptidase C19 family.
CC -!- SIMILARITY: Contains 2 UBA domains.
CC -!- SIMILARITY: Contains 1 UBP-type zinc finger.
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DR EMBL; X91349; CAA62690.1; -; mRNA.
DR EMBL; U47927; AAC50465.1; -; mRNA.
DR EMBL; U47924; AAB51314.1; -; Genomic_DNA.
DR EMBL; U47924; AAB51315.1; -; Genomic_DNA.
DR EMBL; U35116; AAA78934.1; -; mRNA.
DR EMBL; CH471116; EAW88724.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88725.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88726.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88727.1; -; Genomic_DNA.
DR EMBL; BC004889; AAH04889.1; -; mRNA.
DR EMBL; BC005139; AAH05139.1; -; mRNA.
DR PIR; S68227; S68227.
DR RefSeq; NP_001092006.1; NM_001098536.1.
DR RefSeq; NP_003472.2; NM_003481.2.
DR UniGene; Hs.631661; -.
DR PDB; 2DAG; NMR; -; A=655-715.
DR PDB; 2DAK; NMR; -; A=723-772.
DR PDB; 2G43; X-ray; 2.09 A; A/B=163-291.
DR PDB; 2G45; X-ray; 1.99 A; A/D=163-291.
DR PDB; 3IHP; X-ray; 2.80 A; A/B=1-858.
DR PDBsum; 2DAG; -.
DR PDBsum; 2DAK; -.
DR PDBsum; 2G43; -.
DR PDBsum; 2G45; -.
DR PDBsum; 3IHP; -.
DR ProteinModelPortal; P45974; -.
DR SMR; P45974; 1-858.
DR IntAct; P45974; 7.
DR MINT; MINT-5001006; -.
DR STRING; 9606.ENSP00000229268; -.
DR ChEMBL; CHEMBL6158; -.
DR MEROPS; C19.001; -.
DR PhosphoSite; P45974; -.
DR DMDM; 1717869; -.
DR REPRODUCTION-2DPAGE; IPI00375145; -.
DR PaxDb; P45974; -.
DR PRIDE; P45974; -.
DR DNASU; 8078; -.
DR Ensembl; ENST00000229268; ENSP00000229268; ENSG00000111667.
DR Ensembl; ENST00000389231; ENSP00000373883; ENSG00000111667.
DR Ensembl; ENST00000595281; ENSP00000472079; ENSG00000268462.
DR Ensembl; ENST00000597018; ENSP00000470388; ENSG00000268462.
DR GeneID; 8078; -.
DR KEGG; hsa:8078; -.
DR UCSC; uc001qri.4; human.
DR CTD; 8078; -.
DR GeneCards; GC12P007111; -.
DR HGNC; HGNC:12628; USP5.
DR HPA; HPA006756; -.
DR MIM; 601447; gene.
DR neXtProt; NX_P45974; -.
DR PharmGKB; PA37253; -.
DR eggNOG; COG5207; -.
DR HOGENOM; HOG000162311; -.
DR HOVERGEN; HBG002833; -.
DR InParanoid; P45974; -.
DR KO; K11836; -.
DR OMA; LRWEFSM; -.
DR PhylomeDB; P45974; -.
DR ChiTaRS; USP5; human.
DR EvolutionaryTrace; P45974; -.
DR GeneWiki; USP5; -.
DR GenomeRNAi; 8078; -.
DR NextBio; 30687; -.
DR PMAP-CutDB; P45974; -.
DR PRO; PR:P45974; -.
DR ArrayExpress; P45974; -.
DR Bgee; P45974; -.
DR CleanEx; HS_USP5; -.
DR Genevestigator; P45974; -.
DR GO; GO:0005764; C:lysosome; TAS:ProtInc.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0008242; F:omega peptidase activity; IEA:InterPro.
DR GO; GO:0004221; F:ubiquitin thiolesterase activity; TAS:ProtInc.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR018200; Pept_C19ubi-hydrolase_C_CS.
DR InterPro; IPR001394; Peptidase_C19/C67.
DR InterPro; IPR009060; UBA-like.
DR InterPro; IPR015940; UBA/transl_elong_EF1B_N_euk.
DR InterPro; IPR000449; UBA/Ts_N.
DR InterPro; IPR016652; Ubiquitinyl_hydrolase.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001607; Znf_UBP.
DR Pfam; PF00627; UBA; 2.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF02148; zf-UBP; 1.
DR PIRSF; PIRSF016308; UBP; 1.
DR SMART; SM00165; UBA; 2.
DR SMART; SM00290; ZnF_UBP; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR PROSITE; PS50030; UBA; 2.
DR PROSITE; PS00972; UCH_2_1; 1.
DR PROSITE; PS00973; UCH_2_2; 1.
DR PROSITE; PS50235; UCH_2_3; 1.
DR PROSITE; PS50271; ZF_UBP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Hydrolase; Metal-binding;
KW Phosphoprotein; Protease; Reference proteome; Repeat; Thiol protease;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 858 Ubiquitin carboxyl-terminal hydrolase 5.
FT /FTId=PRO_0000080623.
FT DOMAIN 654 695 UBA 1.
FT DOMAIN 722 762 UBA 2.
FT ZN_FING 197 269 UBP-type.
FT REGION 221 224 Substrate binding.
FT ACT_SITE 335 335 Nucleophile.
FT ACT_SITE 818 818 Proton acceptor (By similarity).
FT METAL 199 199 Zinc.
FT METAL 202 202 Zinc.
FT METAL 219 219 Zinc.
FT METAL 232 232 Zinc.
FT BINDING 209 209 Substrate.
FT BINDING 259 259 Substrate.
FT BINDING 261 261 Substrate; via carbonyl oxygen.
FT BINDING 264 264 Substrate.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 623 623 Phosphothreonine (By similarity).
FT MOD_RES 783 783 Phosphoserine.
FT DISULFID 195 816
FT VAR_SEQ 629 652 GSLGFYGNEDEDSFCSPHFSSPTS -> A (in isoform
FT Short).
FT /FTId=VSP_005259.
FT MUTAGEN 199 199 C->A: Decreased rate of activity and
FT decreased zinc binding.
FT MUTAGEN 202 202 C->A: Decreased rate of activity.
FT MUTAGEN 219 219 C->A: Decreased rate of activity.
FT MUTAGEN 221 223 RRY->KWF: Loss of polyubiquitin binding
FT and subsequent activation.
FT MUTAGEN 221 221 R->A: Loss of polyubiquitin hydrolysis.
FT Loss of ubiquitin binding; when
FT associated with A-335.
FT MUTAGEN 232 232 H->A: Decreased rate of activity.
FT MUTAGEN 261 261 Y->F: Loss of polyubiquitin binding.
FT MUTAGEN 335 335 C->A: Loss of activity. Loss of ubiquitin
FT binding; when associated with A-221.
FT Lower affinity for triubiquitin and
FT tetraubiquitin, but no effect on affinity
FT for diubiquitin; when associated with E-
FT 666. Lower affinity for diubiquitin,
FT triubiquitin and tetraubiquitin; when
FT associated with E-734.
FT MUTAGEN 435 435 D->A: Loss of polyubiquitin binding and
FT hydrolysis.
FT MUTAGEN 666 666 M->E: Lower affinity for triubiquitin and
FT tetraubiquitin, but no effect on affinity
FT for diubiquitin; when associated with A-
FT 335. No effect on activity; when
FT associated with E-734.
FT MUTAGEN 734 734 M->E: Lower affinity for diubiquitin,
FT triubiquitin and tetraubiquitin; when
FT associated with A-335. No effect on
FT activity; when associated with E-666.
FT CONFLICT 3 4 EL -> DV (in Ref. 1; CAA62690).
FT CONFLICT 45 45 I -> V (in Ref. 1; CAA62690).
FT CONFLICT 468 468 K -> R (in Ref. 4; AAA78934).
FT CONFLICT 681 681 G -> D (in Ref. 4; AAA78934).
FT HELIX 5 11
FT HELIX 12 15
FT STRAND 31 34
FT STRAND 43 46
FT TURN 47 49
FT TURN 55 57
FT HELIX 58 65
FT STRAND 69 75
FT STRAND 118 124
FT TURN 125 128
FT STRAND 129 131
FT HELIX 141 154
FT TURN 178 182
FT STRAND 200 203
FT STRAND 206 211
FT TURN 212 214
FT STRAND 217 219
FT HELIX 232 240
FT STRAND 244 247
FT STRAND 258 260
FT TURN 261 264
FT STRAND 265 268
FT HELIX 272 277
FT TURN 278 280
FT TURN 283 285
FT HELIX 335 344
FT HELIX 348 354
FT TURN 355 357
FT HELIX 358 364
FT HELIX 369 371
FT HELIX 373 385
FT HELIX 415 421
FT TURN 422 424
FT TURN 426 429
FT STRAND 430 432
FT HELIX 436 449
FT HELIX 457 460
FT STRAND 463 471
FT TURN 472 475
FT STRAND 476 489
FT HELIX 493 495
FT HELIX 499 514
FT HELIX 529 537
FT STRAND 540 547
FT TURN 548 551
FT STRAND 552 564
FT STRAND 567 573
FT STRAND 576 578
FT HELIX 580 582
FT STRAND 584 586
FT STRAND 595 598
FT HELIX 600 602
FT HELIX 658 666
FT HELIX 670 679
FT HELIX 685 695
FT HELIX 700 702
FT HELIX 725 732
FT TURN 733 735
FT HELIX 738 747
FT TURN 748 750
FT HELIX 752 770
FT STRAND 799 812
FT STRAND 818 825
FT STRAND 828 833
FT STRAND 836 839
FT STRAND 849 855
SQ SEQUENCE 858 AA; 95786 MW; E99CB7CDFA682C65 CRC64;
MAELSEEALL SVLPTIRVPK AGDRVHKDEC AFSFDTPESE GGLYICMNTF LGFGKQYVER
HFNKTGQRVY LHLRRTRRPK EEDPATGTGD PPRKKPTRLA IGVEGGFDLS EEKFELDEDV
KIVILPDYLE IARDGLGGLP DIVRDRVTSA VEALLSADSA SRKQEVQAWD GEVRQVSKHA
FSLKQLDNPA RIPPCGWKCS KCDMRENLWL NLTDGSILCG RRYFDGSGGN NHAVEHYRET
GYPLAVKLGT ITPDGADVYS YDEDDMVLDP SLAEHLSHFG IDMLKMQKTD KTMTELEIDM
NQRIGEWELI QESGVPLKPL FGPGYTGIRN LGNSCYLNSV VQVLFSIPDF QRKYVDKLEK
IFQNAPTDPT QDFSTQVAKL GHGLLSGEYS KPVPESGDGE RVPEQKEVQD GIAPRMFKAL
IGKGHPEFST NRQQDAQEFF LHLINMVERN CRSSENPNEV FRFLVEEKIK CLATEKVKYT
QRVDYIMQLP VPMDAALNKE ELLEYEEKKR QAEEEKMALP ELVRAQVPFS SCLEAYGAPE
QVDDFWSTAL QAKSVAVKTT RFASFPDYLV IQIKKFTFGL DWVPKKLDVS IEMPEELDIS
QLRGTGLQPG EEELPDIAPP LVTPDEPKGS LGFYGNEDED SFCSPHFSSP TSPMLDESVI
IQLVEMGFPM DACRKAVYYT GNSGAEAAMN WVMSHMDDPD FANPLILPGS SGPGSTSAAA
DPPPEDCVTT IVSMGFSRDQ ALKALRATNN SLERAVDWIF SHIDDLDAEA AMDISEGRSA
ADSISESVPV GPKVRDGPGK YQLFAFISHM GTSTMCGHYV CHIKKEGRWV IYNDQKVCAS
EKPPKDLGYI YFYQRVAS
//
MIM
601447
*RECORD*
*FIELD* NO
601447
*FIELD* TI
*601447 UBIQUITIN-SPECIFIC PROTEASE 5; USP5
;;ISOPEPTIDASE T; ISOT
*FIELD* TX
DESCRIPTION
read more
Ubiquitin (see 191339)-dependent proteolysis is a complex pathway of
protein metabolism implicated in such diverse cellular functions as
maintenance of chromatin structure, receptor function, and degradation
of abnormal proteins. A late step of the process involves disassembly of
the polyubiquitin chains on degraded proteins into ubiquitin monomers.
USP5 disassembles branched polyubiquitin chains by a sequential exo
mechanism, starting at the proximal end of the chain (Wilkinson et al.,
1995).
CLONING
Wilkinson et al. (1995) purified a 93-kD bovine protein with the
properties expected of a polyubiquitin disassembly protein. They
biochemically characterized the enzyme, which they called isopeptidase T
(ISOT), and cloned a cDNA encoding the human homolog (GenBank U35116).
The deduced 835-amino acid human polypeptide has a predicted molecular
mass of 93.3 kD.
Ansari-Lari et al. (1996) generated the genomic sequence of the human
CD4 gene (186940) and its neighboring region on chromosome 12 using the
large-scale shotgun sequencing strategy. A total of 117 kb of genomic
sequence and approximately 11 kb of cDNA sequence was obtained. They
identified in this sequence 8 genes, including CD4 and ISOT. Using a
battery of strategies, the exon/intron boundaries, splice variants, and
tissue expression patterns of the genes were determined. Tissue
expression analysis indicated a high level of expression of a 3.3-kb
ISOT transcript in brain, and a low level of expression in heart, lung,
spleen, and skeletal muscle. Sequence comparison showed that ISOT is a
member of the ubiquitin C-terminal hydroxylase family. Wilkinson et al.
(1995) originally cloned human ISOT and reported the sequence as 3,102
bp long. Ansari-Lari et al. (1996) stated that comparison of their cDNA
sequence with the sequence reported by Wilkinson et al. (1995) indicated
alternative splicing in exon 15. Four nucleotide differences were found
between the 2 sequences resulting in lys-to-arg and gly-to-asp
substitutions. The cDNA and genomic sequences were in full agreement.
Reyes-Turcu et al. (2006) stated that the 835-amino acid human USP5
protein contains 4 putative ubiquitin-binding domains: an N-terminal
zinc finger ubiquitin-binding domain (ZNF-UBP), a ubiquitin-specific
processing protease (UBP) domain formed by noncontiguous regions
containing the active-site cys and his boxes, and 2 ubiquitin-associated
domains (UBA1 and UBA2). UBA1 and UBA2 are located between the cys and
his boxes, which are in the central and C-terminal regions of USP5,
respectively.
BIOCHEMICAL FEATURES
Reyes-Turcu et al. (2006) reported the crystal structures of the ZNF-UBP
domain of USP5 alone and in complex with ubiquitin at 2.09-angstrom
resolution. They found that, unlike other ubiquitin-binding domains, the
ZNF-UBP domain contains a deep binding pocket where the C-terminal
diglycine motif of ubiquitin is inserted, thus explaining the
specificity of USP5 for an unmodified C terminus on the proximal subunit
of polyubiquitin. Mutation analysis showed that the ZNF-UBP domain was
required for optimal catalytic activation of USP5.
MAPPING
By genomic sequence analysis, Ansari-Lari et al. (1996) mapped the USP5
gene to chromosome 12p13, near the CD4 gene (186940).
*FIELD* RF
1. Ansari-Lari, M. A.; Muzny, D. M.; Lu, J.; Lu, F.; Lilley, C. E.;
Spanos, S.; Malley, T.; Gibbs, R. A.: A gene-rich cluster between
the CD4 and triosephosphate isomerase genes at human chromosome 12p13. Genome
Res. 6: 314-326, 1996.
2. Reyes-Turcu, F. E.; Horton, J. R.; Mullally, J. E.; Heroux, A.;
Cheng, X.; Wilkinson, K. D.: The ubiquitin binding domain ZnF UBP
recognizes the C-terminal diglycine motif of unanchored ubiquitin. Cell 124:
1197-1208, 2006.
3. Wilkinson, K. D.; Tashayev, V. L.; O'Connor, L. B.; Larsen, C.
N.; Kasperek, E.; Pickart, C. M.: Metabolism of the polyubiquitin
degradation signal: structure, mechanism, and role of isopeptidase
T. Biochemistry 34: 14535-14546, 1995.
*FIELD* CN
Matthew B. Gross - updated: 3/3/2010
Mark H. Paalman - updated: 3/20/1997
*FIELD* CD
Victor A. McKusick: 9/26/1996
*FIELD* ED
wwang: 03/05/2010
mgross: 3/3/2010
carol: 5/12/2004
psherman: 2/26/1999
alopez: 2/5/1999
mark: 3/20/1997
terry: 3/20/1997
jamie: 10/23/1996
jamie: 10/16/1996
mark: 9/26/1996
*RECORD*
*FIELD* NO
601447
*FIELD* TI
*601447 UBIQUITIN-SPECIFIC PROTEASE 5; USP5
;;ISOPEPTIDASE T; ISOT
*FIELD* TX
DESCRIPTION
read more
Ubiquitin (see 191339)-dependent proteolysis is a complex pathway of
protein metabolism implicated in such diverse cellular functions as
maintenance of chromatin structure, receptor function, and degradation
of abnormal proteins. A late step of the process involves disassembly of
the polyubiquitin chains on degraded proteins into ubiquitin monomers.
USP5 disassembles branched polyubiquitin chains by a sequential exo
mechanism, starting at the proximal end of the chain (Wilkinson et al.,
1995).
CLONING
Wilkinson et al. (1995) purified a 93-kD bovine protein with the
properties expected of a polyubiquitin disassembly protein. They
biochemically characterized the enzyme, which they called isopeptidase T
(ISOT), and cloned a cDNA encoding the human homolog (GenBank U35116).
The deduced 835-amino acid human polypeptide has a predicted molecular
mass of 93.3 kD.
Ansari-Lari et al. (1996) generated the genomic sequence of the human
CD4 gene (186940) and its neighboring region on chromosome 12 using the
large-scale shotgun sequencing strategy. A total of 117 kb of genomic
sequence and approximately 11 kb of cDNA sequence was obtained. They
identified in this sequence 8 genes, including CD4 and ISOT. Using a
battery of strategies, the exon/intron boundaries, splice variants, and
tissue expression patterns of the genes were determined. Tissue
expression analysis indicated a high level of expression of a 3.3-kb
ISOT transcript in brain, and a low level of expression in heart, lung,
spleen, and skeletal muscle. Sequence comparison showed that ISOT is a
member of the ubiquitin C-terminal hydroxylase family. Wilkinson et al.
(1995) originally cloned human ISOT and reported the sequence as 3,102
bp long. Ansari-Lari et al. (1996) stated that comparison of their cDNA
sequence with the sequence reported by Wilkinson et al. (1995) indicated
alternative splicing in exon 15. Four nucleotide differences were found
between the 2 sequences resulting in lys-to-arg and gly-to-asp
substitutions. The cDNA and genomic sequences were in full agreement.
Reyes-Turcu et al. (2006) stated that the 835-amino acid human USP5
protein contains 4 putative ubiquitin-binding domains: an N-terminal
zinc finger ubiquitin-binding domain (ZNF-UBP), a ubiquitin-specific
processing protease (UBP) domain formed by noncontiguous regions
containing the active-site cys and his boxes, and 2 ubiquitin-associated
domains (UBA1 and UBA2). UBA1 and UBA2 are located between the cys and
his boxes, which are in the central and C-terminal regions of USP5,
respectively.
BIOCHEMICAL FEATURES
Reyes-Turcu et al. (2006) reported the crystal structures of the ZNF-UBP
domain of USP5 alone and in complex with ubiquitin at 2.09-angstrom
resolution. They found that, unlike other ubiquitin-binding domains, the
ZNF-UBP domain contains a deep binding pocket where the C-terminal
diglycine motif of ubiquitin is inserted, thus explaining the
specificity of USP5 for an unmodified C terminus on the proximal subunit
of polyubiquitin. Mutation analysis showed that the ZNF-UBP domain was
required for optimal catalytic activation of USP5.
MAPPING
By genomic sequence analysis, Ansari-Lari et al. (1996) mapped the USP5
gene to chromosome 12p13, near the CD4 gene (186940).
*FIELD* RF
1. Ansari-Lari, M. A.; Muzny, D. M.; Lu, J.; Lu, F.; Lilley, C. E.;
Spanos, S.; Malley, T.; Gibbs, R. A.: A gene-rich cluster between
the CD4 and triosephosphate isomerase genes at human chromosome 12p13. Genome
Res. 6: 314-326, 1996.
2. Reyes-Turcu, F. E.; Horton, J. R.; Mullally, J. E.; Heroux, A.;
Cheng, X.; Wilkinson, K. D.: The ubiquitin binding domain ZnF UBP
recognizes the C-terminal diglycine motif of unanchored ubiquitin. Cell 124:
1197-1208, 2006.
3. Wilkinson, K. D.; Tashayev, V. L.; O'Connor, L. B.; Larsen, C.
N.; Kasperek, E.; Pickart, C. M.: Metabolism of the polyubiquitin
degradation signal: structure, mechanism, and role of isopeptidase
T. Biochemistry 34: 14535-14546, 1995.
*FIELD* CN
Matthew B. Gross - updated: 3/3/2010
Mark H. Paalman - updated: 3/20/1997
*FIELD* CD
Victor A. McKusick: 9/26/1996
*FIELD* ED
wwang: 03/05/2010
mgross: 3/3/2010
carol: 5/12/2004
psherman: 2/26/1999
alopez: 2/5/1999
mark: 3/20/1997
terry: 3/20/1997
jamie: 10/23/1996
jamie: 10/16/1996
mark: 9/26/1996