CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-022954
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Ubiquitin carboxyl-terminal hydrolase 25 
Protein Synonyms/Alias
 Deubiquitinating enzyme 25; USP on chromosome 21; Ubiquitin thioesterase 25; Ubiquitin-specific-processing protease 25 
Gene Name
 USP25 
Gene Synonyms/Alias
 USP21 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
15LQQSAAQKHQQTFLNubiquitination[1]
57AVAFLTAKNAKTPQQubiquitination[1, 2]
60FLTAKNAKTPQQEETubiquitination[2]
99IDLTGDDKDDLQRAIsumoylation[3]
99IDLTGDDKDDLQRAIubiquitination[2]
141EASIAENKACLKRTPsumoylation[3, 4]
201RRLVLNYKPPSNAQDubiquitination[1, 2]
250SRAVEILKDAFKSNDubiquitination[1]
254EILKDAFKSNDSQQQubiquitination[1, 2, 5]
312AVGVLEGKKFENTEMubiquitination[2, 6, 7]
313VGVLEGKKFENTEMFubiquitination[1]
392RPEKIHNKLEFPQVLubiquitination[1]
444LSYGSGPKRFPLVDVubiquitination[1, 2, 7, 8, 9]
520SSRSVIHKPFTQSRIubiquitination[1]
584IELMYSDKSMIQVPYubiquitination[1, 2]
630YNDIAVTKSSWEELVubiquitination[1, 2, 8]
669LIQEEFNKETGQPLVubiquitination[2, 8]
698EDNQRFEKELEEWDAubiquitination[1]
710WDAQLAQKALQEKLLubiquitination[1, 2, 5, 10]
715AQKALQEKLLASQKLubiquitination[1, 2, 5, 9]
721EKLLASQKLRESETSubiquitination[1]
Reference
 [1] 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]
 [2] 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]
 [3] Mechanism and consequences for paralog-specific sumoylation of ubiquitin-specific protease 25.
 Meulmeester E, Kunze M, Hsiao HH, Urlaub H, Melchior F.
 Mol Cell. 2008 Jun 6;30(5):610-9. [PMID: 18538659]
 [4] "ChopNSpice," a mass spectrometric approach that allows identification of endogenous small ubiquitin-like modifier-conjugated peptides.
 Hsiao HH, Meulmeester E, Frank BT, Melchior F, Urlaub H.
 Mol Cell Proteomics. 2009 Dec;8(12):2664-75. [PMID: 19721078]
 [5] 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]
 [6] A data set of human endogenous protein ubiquitination sites.
 Shi Y, Chan DW, Jung SY, Malovannaya A, Wang Y, Qin J.
 Mol Cell Proteomics. 2011 May;10(5):M110.002089. [PMID: 20972266]
 [7] 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]
 [8] 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]
 [9] 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]
 [10] 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] 
Functional Description
 Deubiquitinating enzyme that hydrolyzes ubiquitin moieties conjugated to substrates and thus, functions to process newly synthesized Ubiquitin, to recycle ubiquitin molecules or to edit polyubiquitin chains and prevents proteasomal degradation of substrates. Hydrolyzes both 'Lys-48'- and 'Lys-63'-linked tetraubiquitin chains. 
Sequence Annotation
 DOMAIN 14 57 UBA-like.
 REPEAT 97 116 UIM 1.
 REPEAT 123 140 UIM 2.
 REGION 77 102 SUMO interaction domain (SIM).
 MOTIF 89 95 Required for SUMO paralog-specific
 ACT_SITE 178 178
 ACT_SITE 599 599 By similarity.
 ACT_SITE 607 607 By similarity.
 CROSSLNK 99 99 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 99 99 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 Alternative splicing; Coiled coil; Complete proteome; Cytoplasm; Hydrolase; Isopeptide bond; Nucleus; Phosphoprotein; Protease; Reference proteome; Repeat; Thiol protease; Ubl conjugation; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1055 AA 
Protein Sequence
MTVEQNVLQQ SAAQKHQQTF LNQLREITGI NDTQILQQAL KDSNGNLELA VAFLTAKNAK 60
TPQQEETTYY QTALPGNDRY ISVGSQADTN VIDLTGDDKD DLQRAIALSL AESNRAFRET 120
GITDEEQAIS RVLEASIAEN KACLKRTPTE VWRDSRNPYD RKRQDKAPVG LKNVGNTCWF 180
SAVIQSLFNL LEFRRLVLNY KPPSNAQDLP RNQKEHRNLP FMRELRYLFA LLVGTKRKYV 240
DPSRAVEILK DAFKSNDSQQ QDVSEFTHKL LDWLEDAFQM KAEEETDEEK PKNPMVELFY 300
GRFLAVGVLE GKKFENTEMF GQYPLQVNGF KDLHECLEAA MIEGEIESLH SENSGKSGQE 360
HWFTELPPVL TFELSRFEFN QALGRPEKIH NKLEFPQVLY LDRYMHRNRE ITRIKREEIK 420
RLKDYLTVLQ QRLERYLSYG SGPKRFPLVD VLQYALEFAS SKPVCTSPVD DIDASSPPSG 480
SIPSQTLPST TEQQGALSSE LPSTSPSSVA AISSRSVIHK PFTQSRIPPD LPMHPAPRHI 540
TEEELSVLES CLHRWRTEIE NDTRDLQESI SRIHRTIELM YSDKSMIQVP YRLHAVLVHE 600
GQANAGHYWA YIFDHRESRW MKYNDIAVTK SSWEELVRDS FGGYRNASAY CLMYINDKAQ 660
FLIQEEFNKE TGQPLVGIET LPPDLRDFVE EDNQRFEKEL EEWDAQLAQK ALQEKLLASQ 720
KLRESETSVT TAQAAGDPEY LEQPSRSDFS KHLKEETIQI ITKASHEHED KSPETVLQSA 780
IKLEYARLVK LAQEDTPPET DYRLHHVVVY FIQNQAPKKI IEKTLLEQFG DRNLSFDERC 840
HNIMKVAQAK LEMIKPEEVN LEEYEEWHQD YRKFRETTMY LIIGLENFQR ESYIDSLLFL 900
ICAYQNNKEL LSKGLYRGHD EELISHYRRE CLLKLNEQAA ELFESGEDRE VNNGLIIMNE 960
FIVPFLPLLL VDEMEEKDIL AVEDMRNRWC SYLGQEMEPH LQEKLTDFLP KLLDCSMEIK 1020
SFHEPPKLPS YSTHELCERF ARIMLSLSRT PADGR 1055 
Gene Ontology
 GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0032183; F:SUMO binding; IDA:UniProtKB.
 GO:0004221; F:ubiquitin thiolesterase activity; IEA:InterPro.
 GO:0004843; F:ubiquitin-specific protease activity; IMP:UniProtKB.
 GO:0071108; P:protein K48-linked deubiquitination; IMP:UniProtKB.
 GO:0070536; P:protein K63-linked deubiquitination; IMP:UniProtKB.
 GO:0006508; P:proteolysis; TAS:ProtInc.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro. 
Interpro
 IPR018200; Pept_C19ubi-hydrolase_C_CS.
 IPR001394; Peptidase_C19.
 IPR009060; UBA-like.
 IPR003903; Ubiquitin-int_motif. 
Pfam
 PF00443; UCH
 PF02809; UIM 
SMART
 SM00726; UIM 
PROSITE
 PS00972; UCH_2_1
 PS00973; UCH_2_2
 PS50235; UCH_2_3
 PS50330; UIM 
PRINTS