CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-023836
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Ubiquitin carboxyl-terminal hydrolase 15 
Protein Synonyms/Alias
 Deubiquitinating enzyme 15; Ubiquitin thioesterase 15; Ubiquitin-specific-processing protease 15; Unph-2; Unph4 
Gene Name
 USP15 
Gene Synonyms/Alias
 KIAA0529 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
154VVTRRFSKADTIDTIubiquitination[1, 2, 3]
193NTFEPLNKPDSTIQDubiquitination[4]
228PRGPSTPKSPGASNFubiquitination[1, 3]
259NMNNRNVKNSNYCLPubiquitination[2, 5]
353IKQMWSGKFSYVTPRubiquitination[1, 3, 5]
363YVTPRAFKTQVGRFAubiquitination[2]
605PRNNTEDKLYNLLLLubiquitination[1, 3, 5]
813PWYCPNCKEHQQATKubiquitination[5]
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] 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] 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]
 [4] 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]
 [5] 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] 
Functional Description
 Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling and NF-kappa-B pathways. Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates as well as 'Lys-48'-linked polyubiquitin chains, protecting them against proteasomal degradation. Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP. Protects APC and human papillomavirus type 16 protein E6 against degradation via the ubiquitin proteasome pathway. 
Sequence Annotation
 DOMAIN 7 118 DUSP.
 ACT_SITE 298 298 Nucleophile.
 ACT_SITE 891 891 Proton acceptor (By similarity).
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 229 229 Phosphoserine.
 MOD_RES 242 242 Phosphoserine.
 MOD_RES 961 961 Phosphoserine.
 MOD_RES 965 965 Phosphoserine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Complete proteome; Cytoplasm; Direct protein sequencing; Hydrolase; Nucleus; Phosphoprotein; Protease; Reference proteome; Thiol protease; Ubl conjugation; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 981 AA 
Protein Sequence
MAEGGAADLD TQRSDIATLL KTSLRKGDTW YLVDSRWFKQ WKKYVGFDSW DKYQMGDQNV 60
YPGPIDNSGL LKDGDAQSLK EHLIDELDYI LLPTEGWNKL VSWYTLMEGQ EPIARKVVEQ 120
GMFVKHCKVE VYLTELKLCE NGNMNNVVTR RFSKADTIDT IEKEIRKIFS IPDEKETRLW 180
NKYMSNTFEP LNKPDSTIQD AGLYQGQVLV IEQKNEDGTW PRGPSTPKSP GASNFSTLPK 240
ISPSSLSNNY NNMNNRNVKN SNYCLPSYTA YKNYDYSEPG RNNEQPGLCG LSNLGNTCFM 300
NSAIQCLSNT PPLTEYFLND KYQEELNFDN PLGMRGEIAK SYAELIKQMW SGKFSYVTPR 360
AFKTQVGRFA PQFSGYQQQD CQELLAFLLD GLHEDLNRIR KKPYIQLKDA DGRPDKVVAE 420
EAWENHLKRN DSIIVDIFHG LFKSTLVCPE CAKISVTFDP FCYLTLPLPM KKERTLEVYL 480
VRMDPLTKPM QYKVVVPKIG NILDLCTALS ALSGIPADKM IVTDIYNHRF HRIFAMDENL 540
SSIMERDDIY VFEININRTE DTEHVIIPVC LREKFRHSSY THHTGSSLFG QPFLMAVPRN 600
NTEDKLYNLL LLRMCRYVKI STETEETEGS LHCCKDQNIN GNGPNGIHEE GSPSEMETDE 660
PDDESSQDQE LPSENENSQS EDSVGGDNDS ENGLCTEDTC KGQLTGHKKR LFTFQFNNLG 720
NTDINYIKDD TRHIRFDDRQ LRLDERSFLA LDWDPDLKKR YFDENAAEDF EKHESVEYKP 780
PKKPFVKLKD CIELFTTKEK LGAEDPWYCP NCKEHQQATK KLDLWSLPPV LVVHLKRFSY 840
SRYMRDKLDT LVDFPINDLD MSEFLINPNA GPCRYNLIAV SNHYGGMGGG HYTAFAKNKD 900
DGKWYYFDDS SVSTASEDQI VSKAAYVLFY QRQDTFSGTG FFPLDRETKG ASAATGIPLE 960
SDEDSNDNDN DIENENCMHT N 981 
Gene Ontology
 GO:0005737; C:cytoplasm; IDA:UniProtKB.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0004197; F:cysteine-type endopeptidase activity; IMP:UniProtKB.
 GO:0004221; F:ubiquitin thiolesterase activity; IDA:UniProtKB.
 GO:0004843; F:ubiquitin-specific protease activity; IDA:UniProtKB.
 GO:0030509; P:BMP signaling pathway; IDA:UniProtKB.
 GO:0035520; P:monoubiquitinated protein deubiquitination; IDA:UniProtKB.
 GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:Reactome.
 GO:0060389; P:pathway-restricted SMAD protein phosphorylation; IMP:UniProtKB.
 GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro. 
Interpro
 IPR006615; Pept_C19_DUSP.
 IPR018200; Pept_C19ubi-hydrolase_C_CS.
 IPR001394; Peptidase_C19.
 IPR013792; RNA3'P_cycl/enolpyr_Trfase_a/b. 
Pfam
 PF06337; DUSP
 PF00443; UCH 
SMART
 SM00695; DUSP 
PROSITE
 PS51283; DUSP
 PS00972; UCH_2_1
 PS00973; UCH_2_2
 PS50235; UCH_2_3 
PRINTS