CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-019606
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Ubiquitin carboxyl-terminal hydrolase 28 
Protein Synonyms/Alias
 Deubiquitinating enzyme 28; Ubiquitin thioesterase 28; Ubiquitin-specific-processing protease 28 
Gene Name
 USP28 
Gene Synonyms/Alias
 KIAA1515 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
64LLTDERVKEPSQDTVubiquitination[1]
243SAALDLLKGAFRSSEubiquitination[1, 2, 3, 4]
381QSLGQPEKIHNKLEFubiquitination[3]
839FFQNEAPKRVVERTLubiquitination[1]
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] 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]
 [3] 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]
 [4] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 
Functional Description
 Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus. 
Sequence Annotation
 REPEAT 97 116 UIM.
 ACT_SITE 171 171 Nucleophile.
 ACT_SITE 600 600 Proton acceptor (By similarity).
 MOD_RES 67 67 Phosphoserine.
 MOD_RES 714 714 Phosphoserine.  
Keyword
 3D-structure; Alternative splicing; Complete proteome; DNA damage; DNA repair; Hydrolase; Nucleus; Phosphoprotein; Protease; Reference proteome; Thiol protease; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1077 AA 
Protein Sequence
MTAELQQDDA AGAADGHGSS CQMLLNQLRE ITGIQDPSFL HEALKASNGD ITQAVSLLTD 60
ERVKEPSQDT VATEPSEVEG SAANKEVLAK VIDLTHDNKD DLQAAIALSL LESPKIQADG 120
RDLNRMHEAT SAETKRSKRK RCEVWGENPN PNDWRRVDGW PVGLKNVGNT CWFSAVIQSL 180
FQLPEFRRLV LSYSLPQNVL ENCRSHTEKR NIMFMQELQY LFALMMGSNR KFVDPSAALD 240
LLKGAFRSSE EQQQDVSEFT HKLLDWLEDA FQLAVNVNSP RNKSENPMVQ LFYGTFLTEG 300
VREGKPFCNN ETFGQYPLQV NGYRNLDECL EGAMVEGDVE LLPSDHSVKY GQERWFTKLP 360
PVLTFELSRF EFNQSLGQPE KIHNKLEFPQ IIYMDRYMYR SKELIRNKRE CIRKLKEEIK 420
ILQQKLERYV KYGSGPARFP LPDMLKYVIE FASTKPASES CPPESDTHMT LPLSSVHCSV 480
SDQTSKESTS TESSSQDVES TFSSPEDSLP KSKPLTSSRS SMEMPSQPAP RTVTDEEINF 540
VKTCLQRWRS EIEQDIQDLK TCIASTTQTI EQMYCDPLLR QVPYRLHAVL VHEGQANAGH 600
YWAYIYNQPR QSWLKYNDIS VTESSWEEVE RDSYGGLRNV SAYCLMYIND KLPYFNAEAA 660
PTESDQMSEV EALSVELKHY IQEDNWRFEQ EVEEWEEEQS CKIPQMESST NSSSQDYSTS 720
QEPSVASSHG VRCLSSEHAV IVKEQTAQAI ANTARAYEKS GVEAALSEVM LSPAMQGVIL 780
AIAKARQTFD RDGSEAGLIK AFHEEYSRLY QLAKETPTSH SDPRLQHVLV YFFQNEAPKR 840
VVERTLLEQF ADKNLSYDER SISIMKVAQA KLKEIGPDDM NMEEYKKWHE DYSLFRKVSV 900
YLLTGLELYQ KGKYQEALSY LVYAYQSNAA LLMKGPRRGV KESVIALYRR KCLLELNAKA 960
ASLFETNDDH SVTEGINVMN ELIIPCIHLI INNDISKDDL DAIEVMRNHW CSYLGQDIAE 1020
NLQLCLGEFL PRLLDPSAEI IVLKEPPTIR PNSPYDLCSR FAAVMESIQG VSTVTVK 1077 
Gene Ontology
 GO:0005730; C:nucleolus; IDA:HPA.
 GO:0005654; C:nucleoplasm; IDA:UniProtKB.
 GO:0043234; C:protein complex; IDA:UniProtKB.
 GO:0004221; F:ubiquitin thiolesterase activity; IMP:UniProtKB.
 GO:0004843; F:ubiquitin-specific protease activity; IDA:UniProtKB.
 GO:0008283; P:cell proliferation; IMP:UniProtKB.
 GO:0034644; P:cellular response to UV; IDA:UniProtKB.
 GO:0000077; P:DNA damage checkpoint; IMP:UniProtKB.
 GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
 GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IDA:UniProtKB.
 GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
 GO:0010212; P:response to ionizing radiation; IDA:UniProtKB.
 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 
SMART
 SM00726; UIM 
PROSITE
 PS00972; UCH_2_1
 PS00973; UCH_2_2
 PS50235; UCH_2_3
 PS50330; UIM 
PRINTS