CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012376
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Ubiquitin carboxyl-terminal hydrolase 10 
Protein Synonyms/Alias
 Deubiquitinating enzyme 10; Ubiquitin thioesterase 10; Ubiquitin-specific-processing protease 10 
Gene Name
 USP10 
Gene Synonyms/Alias
 KIAA0190 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
408ENVTLIHKPVSLQPRubiquitination[1, 2]
714PVDLEISKELLSPGVacetylation[3, 4]
714PVDLEISKELLSPGVubiquitination[5, 6]
780INQYQVVKPTAERTAubiquitination[5, 6, 7]
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] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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]
 [7] 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] 
Functional Description
 Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, BECN1, SNX3 and CFTR. Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53. Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response. Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34- containing complexes. In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Does not deubiquitinate MDM2. Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling. 
Sequence Annotation
 REGION 2 100 Interaction with p53/TP53.
 ACT_SITE 424 424 Nucleophile.
 ACT_SITE 749 749 Proton acceptor (By similarity).
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 24 24 Phosphothreonine.
 MOD_RES 42 42 Phosphothreonine; by ATM.
 MOD_RES 100 100 Phosphothreonine.
 MOD_RES 208 208 Phosphothreonine (By similarity).
 MOD_RES 226 226 Phosphoserine.
 MOD_RES 337 337 Phosphoserine; by ATM.
 MOD_RES 365 365 Phosphoserine.
 MOD_RES 370 370 Phosphoserine.
 MOD_RES 563 563 Phosphoserine.
 MOD_RES 576 576 Phosphoserine.  
Keyword
 Acetylation; Alternative splicing; Autophagy; Complete proteome; Cytoplasm; DNA damage; DNA repair; Endosome; Hydrolase; Nucleus; Phosphoprotein; Polymorphism; Protease; Reference proteome; Thiol protease; Ubl conjugation; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 798 AA 
Protein Sequence
MALHSPQYIF GDFSPDEFNQ FFVTPRSSVE LPPYSGTVLC GTQAVDKLPD GQEYQRIEFG 60
VDEVIEPSDT LPRTPSYSIS STLNPQAPEF ILGCTASKIT PDGITKEASY GSIDCQYPGS 120
ALALDGSSNV EAEVLENDGV SGGLGQRERK KKKKRPPGYY SYLKDGGDDS ISTEALVNGH 180
ANSAVPNSVS AEDAEFMGDM PPSVTPRTCN SPQNSTDSVS DIVPDSPFPG ALGSDTRTAG 240
QPEGGPGADF GQSCFPAEAG RDTLSRTAGA QPCVGTDTTE NLGVANGQIL ESSGEGTATN 300
GVELHTTESI DLDPTKPESA SPPADGTGSA SGTLPVSQPK SWASLFHDSK PSSSSPVAYV 360
ETKYSPPAIS PLVSEKQVEV KEGLVPVSED PVAIKIAELL ENVTLIHKPV SLQPRGLINK 420
GNWCYINATL QALVACPPMY HLMKFIPLYS KVQRPCTSTP MIDSFVRLMN EFTNMPVPPK 480
PRQALGDKIV RDIRPGAAFE PTYIYRLLTV NKSSLSEKGR QEDAEEYLGF ILNGLHEEML 540
NLKKLLSPSN EKLTISNGPK NHSVNEEEQE EQGEGSEDEW EQVGPRNKTS VTRQADFVQT 600
PITGIFGGHI RSVVYQQSSK ESATLQPFFT LQLDIQSDKI RTVQDALESL VARESVQGYT 660
TKTKQEVEIS RRVTLEKLPP VLVLHLKRFV YEKTGGCQKL IKNIEYPVDL EISKELLSPG 720
VKNKNFKCHR TYRLFAVVYH HGNSATGGHY TTDVFQIGLN GWLRIDDQTV KVINQYQVVK 780
PTAERTAYLL YYRRVDLL 798 
Gene Ontology
 GO:0005769; C:early endosome; IDA:UniProtKB.
 GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0004197; F:cysteine-type endopeptidase activity; IMP:UniProtKB.
 GO:0044325; F:ion channel binding; IDA:UniProtKB.
 GO:0004221; F:ubiquitin thiolesterase activity; IDA:UniProtKB.
 GO:0004843; F:ubiquitin-specific protease activity; IDA:UniProtKB.
 GO:0006914; P:autophagy; IEA:UniProtKB-KW.
 GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IMP:UniProtKB.
 GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
 GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
 GO:0010506; P:regulation of autophagy; IDA:UniProtKB.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro. 
Interpro
 IPR009818; Ataxin-2_C.
 IPR018200; Pept_C19ubi-hydrolase_C_CS.
 IPR001394; Peptidase_C19. 
Pfam
 PF07145; PAM2
 PF00443; UCH 
SMART
  
PROSITE
 PS00972; UCH_2_1
 PS00973; UCH_2_2
 PS50235; UCH_2_3 
PRINTS