CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007413
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Ubiquitin carboxyl-terminal hydrolase 8 
Protein Synonyms/Alias
 Deubiquitinating enzyme 8; Ubiquitin isopeptidase Y; hUBPy; Ubiquitin thioesterase 8; Ubiquitin-specific-processing protease 8 
Gene Name
 USP8 
Gene Synonyms/Alias
 KIAA0055; UBPY 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
538EQAKKEDKETSAKRGacetylation[1]
601TGDSGSGKPFKIKGQacetylation[2, 3]
Reference
 [1] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [2] 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]
 [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] 
Functional Description
 Hydrolase that can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation. Converts both 'Lys-48' an 'Lys-63'-linked ubiquitin chains. Catalytic activity is enhanced in the M phase. Involved in cell proliferation. Required to enter into S phase in response to serum stimulation. May regulate T-cell anergy mediated by RNF128 via the formation of a complex containing RNF128 and OTUB1. Probably regulates the stability of STAM2 and RASGRF1. Regulates endosomal ubiquitin dynamics, cargo sorting, membrane traffic at early endosomes, and maintenance of ESCRT-0 stability. The level of protein ubiquitination on endosomes is essential for maintaining the morphology of the organelle. Deubiquitinates EPS15 and controles tyrosine kinase stability. Removes conjugated ubiquitin from EGFR thus regulating EGFR degradation and downstream MAPK signaling. Involved in acrosome biogenesis through interaction with the spermatid ESCRT-0 complex and microtubules. Deubiquitinates BIRC6/bruce and KIF23/MKLP1. 
Sequence Annotation
 DOMAIN 33 116 MIT.
 DOMAIN 195 313 Rhodanese.
 MOTIF 405 413 SH3-binding (By similarity).
 ACT_SITE 786 786 Nucleophile (By similarity).
 ACT_SITE 1067 1067 Proton acceptor (By similarity).
 MOD_RES 160 160 Phosphoserine.
 MOD_RES 452 452 Phosphoserine.
 MOD_RES 577 577 Phosphothreonine.
 MOD_RES 718 718 Phosphoserine.
 MOD_RES 719 719 Phosphoserine.
 MOD_RES 945 945 Phosphothreonine (By similarity).  
Keyword
 3D-structure; Cell cycle; Cell membrane; Complete proteome; Cytoplasm; Endosome; Hydrolase; Membrane; Nucleus; Phosphoprotein; Polymorphism; Protease; Reference proteome; SH3-binding; Thiol protease; Ubl conjugation; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1118 AA 
Protein Sequence
MPAVASVPKE LYLSSSLKDL NKKTEVKPEK ISTKSYVHSA LKIFKTAEEC RLDRDEERAY 60
VLYMKYVTVY NLIKKRPDFK QQQDYFHSIL GPGNIKKAVE EAERLSESLK LRYEEAEVRK 120
KLEEKDRQEE AQRLQQKRQE TGREDGGTLA KGSLENVLDS KDKTQKSNGE KNEKCETKEK 180
GAITAKELYT MMTDKNISLI IMDARRMQDY QDSCILHSLS VPEEAISPGV TASWIEAHLP 240
DDSKDTWKKR GNVEYVVLLD WFSSAKDLQI GTTLRSLKDA LFKWESKTVL RNEPLVLEGG 300
YENWLLCYPQ YTTNAKVTPP PRRQNEEVSI SLDFTYPSLE ESIPSKPAAQ TPPASIEVDE 360
NIELISGQNE RMGPLNISTP VEPVAASKSD VSPIIQPVPS IKNVPQIDRT KKPAVKLPEE 420
HRIKSESTNH EQQSPQSGKV IPDRSTKPVV FSPTLMLTDE EKARIHAETA LLMEKNKQEK 480
ELRERQQEEQ KEKLRKEEQE QKAKKKQEAE ENEITEKQQK AKEEMEKKES EQAKKEDKET 540
SAKRGKEITG VKRQSKSEHE TSDAKKSVED RGKRCPTPEI QKKSTGDVPH TSVTGDSGSG 600
KPFKIKGQPE SGILRTGTFR EDTDDTERNK AQREPLTRAR SEEMGRIVPG LPSGWAKFLD 660
PITGTFRYYH SPTNTVHMYP PEMAPSSAPP STPPTHKAKP QIPAERDREP SKLKRSYSSP 720
DITQAIQEEE KRKPTVTPTV NRENKPTCYP KAEISRLSAS QIRNLNPVFG GSGPALTGLR 780
NLGNTCYMNS ILQCLCNAPH LADYFNRNCY QDDINRSNLL GHKGEVAEEF GIIMKALWTG 840
QYRYISPKDF KITIGKINDQ FAGYSQQDSQ ELLLFLMDGL HEDLNKADNR KRYKEENNDH 900
LDDFKAAEHA WQKHKQLNES IIVALFQGQF KSTVQCLTCH KKSRTFEAFM YLSLPLASTS 960
KCTLQDCLRL FSKEEKLTDN NRFYCSHCRA RRDSLKKIEI WKLPPVLLVH LKRFSYDGRW 1020
KQKLQTSVDF PLENLDLSQY VIGPKNNLKK YNLFSVSNHY GGLDGGHYTA YCKNAARQRW 1080
FKFDDHEVSD ISVSSVKSSA AYILFYTSLG PRVTDVAT 1118 
Gene Ontology
 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0005769; C:early endosome; IDA:UniProtKB.
 GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
 GO:0019897; C:extrinsic to plasma membrane; IDA:UniProtKB.
 GO:0030496; C:midbody; IDA:MGI.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc.
 GO:0004221; F:ubiquitin thiolesterase activity; IEA:InterPro.
 GO:0004843; F:ubiquitin-specific protease activity; IDA:UniProtKB.
 GO:0008283; P:cell proliferation; TAS:ProtInc.
 GO:0007032; P:endosome organization; IMP:UniProtKB.
 GO:0000281; P:mitotic cytokinesis; IMP:MGI.
 GO:0071108; P:protein K48-linked deubiquitination; IDA:UniProtKB.
 GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB.
 GO:0007265; P:Ras protein signal transduction; IEA:Compara.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro. 
Interpro
 IPR015063; DUF1873.
 IPR018200; Pept_C19ubi-hydrolase_C_CS.
 IPR001394; Peptidase_C19.
 IPR001763; Rhodanese-like_dom. 
Pfam
 PF08969; DUF1873
 PF00581; Rhodanese
 PF00443; UCH 
SMART
 SM00450; RHOD 
PROSITE
 PS50206; RHODANESE_3
 PS00972; UCH_2_1
 PS00973; UCH_2_2
 PS50235; UCH_2_3 
PRINTS