CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007760
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Ubiquitin carboxyl-terminal hydrolase 5 
Protein Synonyms/Alias
 Deubiquitinating enzyme 5; Isopeptidase T; Ubiquitin thioesterase 5; Ubiquitin-specific-processing protease 5 
Gene Name
 USP5 
Gene Synonyms/Alias
 ISOT 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
20LPTIRVPKAGDRVHKubiquitination[1, 2]
27KAGDRVHKDECAFSFubiquitination[1]
64YVERHFNKTGQRVYLubiquitination[1]
80LRRTRRPKEEDPATGubiquitination[2]
163SADSASRKQEVQAWDubiquitination[1, 2, 3, 4, 5]
178GEVRQVSKHAFSLKQubiquitination[2]
184SKHAFSLKQLDNPARacetylation[6, 7, 8]
184SKHAFSLKQLDNPARubiquitination[1, 2, 3, 4, 5, 9, 10, 11, 12]
247TGYPLAVKLGTITPDubiquitination[4]
291LKMQKTDKTMTELEIubiquitination[2]
318QESGVPLKPLFGPGYubiquitination[1, 2, 3, 4, 5, 9, 10, 11]
353SIPDFQRKYVDKLEKacetylation[5]
353SIPDFQRKYVDKLEKubiquitination[1, 2, 3, 4, 5, 10]
357FQRKYVDKLEKIFQNacetylation[7]
357FQRKYVDKLEKIFQNubiquitination[1, 2, 3, 4, 5, 9, 10, 13]
360KYVDKLEKIFQNAPTubiquitination[1, 2, 3, 4, 5, 9, 10, 12, 13, 14, 15]
379DFSTQVAKLGHGLLSubiquitination[4]
391LLSGEYSKPVPESGDubiquitination[1, 2, 4, 5, 10]
406GERVPEQKEVQDGIAubiquitination[1, 5, 10]
418GIAPRMFKALIGKGHubiquitination[1, 2, 4, 5, 10]
423MFKALIGKGHPEFSTubiquitination[1, 2, 3, 4, 5, 9, 11, 12, 13]
468FRFLVEEKIKCLATEubiquitination[1, 2, 5, 10]
470FLVEEKIKCLATEKVubiquitination[2, 9]
476IKCLATEKVKYTQRVubiquitination[1, 2, 4, 12]
478CLATEKVKYTQRVDYubiquitination[2]
499PMDAALNKEELLEYEubiquitination[1, 4]
516KRQAEEEKMALPELVubiquitination[2]
553WSTALQAKSVAVKTTubiquitination[2, 5, 10]
558QAKSVAVKTTRFASFubiquitination[1, 2, 3, 4, 5, 10]
574DYLVIQIKKFTFGLDubiquitination[1, 3, 4, 5, 9, 10]
575YLVIQIKKFTFGLDWubiquitination[1, 2, 3, 4, 9, 12]
585FGLDWVPKKLDVSIEubiquitination[1, 4]
586GLDWVPKKLDVSIEMubiquitination[1, 2, 4, 5, 10]
743FSRDQALKALRATNNubiquitination[1, 2, 3, 4, 5, 9, 10, 12, 15]
793ESVPVGPKVRDGPGKubiquitination[1, 2, 3, 4, 5, 9, 10, 11, 12, 13, 14, 15]
836WVIYNDQKVCASEKPubiquitination[2, 5, 9, 10, 12]
845CASEKPPKDLGYIYFubiquitination[5, 9]
Reference
 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [4] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [5] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [6] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [7] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [8] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [9] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [10] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [11] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [12] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [13] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [14] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [15] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931
Functional Description
 Cleaves linear and branched multiubiquitin polymers with a marked preference for branched polymers. Involved in unanchored 'Lys-48'-linked polyubiquitin disassembly. Binds linear and 'Lys- 63'-linked polyubiquitin with a lower affinity. Knock-down of USP5 causes the accumulation of p53/TP53 and an increase in p53/TP53 transcriptional activity because the unanchored polyubiquitin that accumulates is able to compete with ubiquitinated p53/TP53 but not with MDM2 for proteasomal recognition. 
Sequence Annotation
 DOMAIN 654 695 UBA 1.
 DOMAIN 722 762 UBA 2.
 ZN_FING 197 269 UBP-type.
 REGION 221 224 Substrate binding.
 ACT_SITE 335 335 Nucleophile.
 ACT_SITE 818 818 Proton acceptor (By similarity).
 METAL 199 199 Zinc.
 METAL 202 202 Zinc.
 METAL 219 219 Zinc.
 METAL 232 232 Zinc.
 BINDING 209 209 Substrate.
 BINDING 259 259 Substrate.
 BINDING 261 261 Substrate; via carbonyl oxygen.
 BINDING 264 264 Substrate.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 623 623 Phosphothreonine (By similarity).
 MOD_RES 783 783 Phosphoserine.
 DISULFID 195 816  
Keyword
 3D-structure; Acetylation; Alternative splicing; Complete proteome; Direct protein sequencing; Disulfide bond; Hydrolase; Metal-binding; Phosphoprotein; Protease; Reference proteome; Repeat; Thiol protease; Ubl conjugation pathway; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 858 AA 
Protein Sequence
MAELSEEALL SVLPTIRVPK AGDRVHKDEC AFSFDTPESE GGLYICMNTF LGFGKQYVER 60
HFNKTGQRVY LHLRRTRRPK EEDPATGTGD PPRKKPTRLA IGVEGGFDLS EEKFELDEDV 120
KIVILPDYLE IARDGLGGLP DIVRDRVTSA VEALLSADSA SRKQEVQAWD GEVRQVSKHA 180
FSLKQLDNPA RIPPCGWKCS KCDMRENLWL NLTDGSILCG RRYFDGSGGN NHAVEHYRET 240
GYPLAVKLGT ITPDGADVYS YDEDDMVLDP SLAEHLSHFG IDMLKMQKTD KTMTELEIDM 300
NQRIGEWELI QESGVPLKPL FGPGYTGIRN LGNSCYLNSV VQVLFSIPDF QRKYVDKLEK 360
IFQNAPTDPT QDFSTQVAKL GHGLLSGEYS KPVPESGDGE RVPEQKEVQD GIAPRMFKAL 420
IGKGHPEFST NRQQDAQEFF LHLINMVERN CRSSENPNEV FRFLVEEKIK CLATEKVKYT 480
QRVDYIMQLP VPMDAALNKE ELLEYEEKKR QAEEEKMALP ELVRAQVPFS SCLEAYGAPE 540
QVDDFWSTAL QAKSVAVKTT RFASFPDYLV IQIKKFTFGL DWVPKKLDVS IEMPEELDIS 600
QLRGTGLQPG EEELPDIAPP LVTPDEPKGS LGFYGNEDED SFCSPHFSSP TSPMLDESVI 660
IQLVEMGFPM DACRKAVYYT GNSGAEAAMN WVMSHMDDPD FANPLILPGS SGPGSTSAAA 720
DPPPEDCVTT IVSMGFSRDQ ALKALRATNN SLERAVDWIF SHIDDLDAEA AMDISEGRSA 780
ADSISESVPV GPKVRDGPGK YQLFAFISHM GTSTMCGHYV CHIKKEGRWV IYNDQKVCAS 840
EKPPKDLGYI YFYQRVAS 858 
Gene Ontology
 GO:0005764; C:lysosome; TAS:ProtInc.
 GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc.
 GO:0008242; F:omega peptidase activity; IEA:InterPro.
 GO:0004221; F:ubiquitin thiolesterase activity; TAS:ProtInc.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
 GO:0071108; P:protein K48-linked deubiquitination; IMP:UniProtKB.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro. 
Interpro
 IPR018200; Pept_C19ubi-hydrolase_C_CS.
 IPR001394; Peptidase_C19.
 IPR009060; UBA-like.
 IPR000449; UBA/transl_elong_EF1B_N.
 IPR015940; UBA/transl_elong_EF1B_N_euk.
 IPR016652; Ubiquitinyl_hydrolase.
 IPR013083; Znf_RING/FYVE/PHD.
 IPR001607; Znf_UBP. 
Pfam
 PF00627; UBA
 PF00443; UCH
 PF02148; zf-UBP 
SMART
 SM00165; UBA
 SM00290; ZnF_UBP 
PROSITE
 PS50030; UBA
 PS00972; UCH_2_1
 PS00973; UCH_2_2
 PS50235; UCH_2_3
 PS50271; ZF_UBP 
PRINTS