CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-008871
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Ubiquitin carboxyl-terminal hydrolase 14 
Protein Synonyms/Alias
 Deubiquitinating enzyme 14; Ubiquitin thioesterase 14; Ubiquitin-specific-processing protease 14 
Gene Name
 USP14 
Gene Synonyms/Alias
 TGT 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
49ARQKVMVKGGTLKDDubiquitination[1, 2]
54MVKGGTLKDDDWGNIubiquitination[2]
62DDDWGNIKIKNGMTLubiquitination[1, 2, 3, 4]
130IRSVPELKDALKRYAubiquitination[1, 2]
134PELKDALKRYAGALRubiquitination[2]
214MMRVLQQKLEAIEDDubiquitination[1, 2, 3, 4]
224AIEDDSVKETDSSSAubiquitination[2, 3, 4]
238ASAATPSKKKSLIDQubiquitination[2, 3, 4]
267SEEEEVTKGKENQLQubiquitination[2]
269EEEVTKGKENQLQLSubiquitination[2]
291KYLFTGLKLRLQEEIacetylation[5]
291KYLFTGLKLRLQEEIubiquitination[1, 2, 3, 4]
300RLQEEITKQSPTLQRubiquitination[1, 2, 3, 4, 6]
313QRNALYIKSSKISRLacetylation[5]
313QRNALYIKSSKISRLubiquitination[2, 3, 4]
334QMVRFFYKEKESVNAubiquitination[2]
336VRFFYKEKESVNAKVubiquitination[2]
342EKESVNAKVLKDVKFubiquitination[2, 3]
345SVNAKVLKDVKFPLMubiquitination[2]
348AKVLKDVKFPLMLDMubiquitination[2]
375VSFRSKFKDLEDKKVubiquitination[2]
380KFKDLEDKKVNQQPNubiquitination[1, 2]
400SSPQKEVKYEPFSFAubiquitination[2]
441GHYVSWVKRKQDEWIubiquitination[1, 2, 3, 4, 7]
443YVSWVKRKQDEWIKFubiquitination[1]
449RKQDEWIKFDDDKVSacetylation[5]
449RKQDEWIKFDDDKVSubiquitination[1, 2, 3, 4]
454WIKFDDDKVSIVTPEubiquitination[3, 4, 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] 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] 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]
 [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] 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]
 [6] 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]
 [7] 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] 
Functional Description
 Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins. Ensures the regeneration of ubiquitin at the proteasome. Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell. Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis. Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1. Indispensable for synaptic development and function at neuromuscular junctions (NMJs). 
Sequence Annotation
 DOMAIN 4 80 Ubiquitin-like.
 ACT_SITE 114 114 Nucleophile (Probable).
 ACT_SITE 435 435 Proton acceptor (By similarity).
 MOD_RES 136 136 Phosphotyrosine (By similarity).
 MOD_RES 143 143 Phosphoserine.
 MOD_RES 222 222 Phosphoserine (By similarity).
 MOD_RES 235 235 Phosphothreonine.
 MOD_RES 449 449 N6-acetyllysine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Cell membrane; Complete proteome; Cytoplasm; Hydrolase; Membrane; Phosphoprotein; Protease; Proteasome; Reference proteome; Thiol protease; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 494 AA 
Protein Sequence
MPLYSVTVKW GKEKFEGVEL NTDEPPMVFK AQLFALTGVQ PARQKVMVKG GTLKDDDWGN 60
IKIKNGMTLL MMGSADALPE EPSAKTVFVE DMTEEQLASA MELPCGLTNL GNTCYMNATV 120
QCIRSVPELK DALKRYAGAL RASGEMASAQ YITAALRDLF DSMDKTSSSI PPIILLQFLH 180
MAFPQFAEKG EQGQYLQQDA NECWIQMMRV LQQKLEAIED DSVKETDSSS ASAATPSKKK 240
SLIDQFFGVE FETTMKCTES EEEEVTKGKE NQLQLSCFIN QEVKYLFTGL KLRLQEEITK 300
QSPTLQRNAL YIKSSKISRL PAYLTIQMVR FFYKEKESVN AKVLKDVKFP LMLDMYELCT 360
PELQEKMVSF RSKFKDLEDK KVNQQPNTSD KKSSPQKEVK YEPFSFADDI GSNNCGYYDL 420
QAVLTHQGRS SSSGHYVSWV KRKQDEWIKF DDDKVSIVTP EDILRLSGGG DWHIAYVLLY 480
GPRRVEIMEE ESEQ 494 
Gene Ontology
 GO:0009986; C:cell surface; IDA:UniProtKB.
 GO:0016023; C:cytoplasmic membrane-bounded vesicle; IDA:UniProtKB.
 GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
 GO:0000502; C:proteasome complex; IEA:UniProtKB-KW.
 GO:0045202; C:synapse; IEA:Compara.
 GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc.
 GO:0004866; F:endopeptidase inhibitor activity; IMP:UniProtKB.
 GO:0070628; F:proteasome binding; IDA:UniProtKB.
 GO:0008193; F:tRNA guanylyltransferase activity; TAS:ProtInc.
 GO:0004221; F:ubiquitin thiolesterase activity; IDA:UniProtKB.
 GO:0004843; F:ubiquitin-specific protease activity; TAS:ProtInc.
 GO:0050920; P:regulation of chemotaxis; IMP:UniProtKB.
 GO:0061136; P:regulation of proteasomal protein catabolic process; IMP:UniProtKB.
 GO:0007268; P:synaptic transmission; IEA:Compara.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro. 
Interpro
 IPR018200; Pept_C19ubi-hydrolase_C_CS.
 IPR001394; Peptidase_C19.
 IPR000626; Ubiquitin.
 IPR019954; Ubiquitin_CS.
 IPR019955; Ubiquitin_supergroup. 
Pfam
 PF00443; UCH 
SMART
 SM00213; UBQ 
PROSITE
 PS00299; UBIQUITIN_1
 PS50053; UBIQUITIN_2
 PS00972; UCH_2_1
 PS00973; UCH_2_2
 PS50235; UCH_2_3 
PRINTS