EzCatDB: S00524
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DB codeS00524
RLCP classification1.12.30000.45 : Hydrolysis
1.13.30000.45 : Hydrolysis
1.14.30000.45 : Hydrolysis
CATH domainDomain 13.40.532.10 : Ubiquitin C-terminal Hydrolase UCH-l3Catalytic domain
E.C.3.1.2.15,3.4.19.12
CSA1cmx,1uch


Enzyme Name
UniProtKBKEGG

P35127P15374
Protein nameUbiquitin carboxyl-terminal hydrolase YUH1Ubiquitin carboxyl-terminal hydrolase isozyme L3ubiquitin thiolesterase
   (EC 3.1.2.15)
ubiquitin carboxy-terminal esterase
   (EC 3.1.2.15)
isopeptidase
   (EC 3.1.2.15)
isopeptidase T
   (EC 3.1.2.15)
ubiquitin C-terminal hydrolase
   (EC 3.1.2.15)
ubiquitin carboxy-terminal hydrolase
   (EC 3.1.2.15)
ubiquitin-C-terminal-thiolester hydrolase
   (EC 3.1.2.15)
ubiquitinyl hydrolase 1
   (EC 3.4.19.12)
ubiquitin C-terminal hydrolase
   (EC 3.4.19.12)
yeast ubiquitin hydrolase
   (EC 3.4.19.12)
SynonymsUCH
EC 3.4.19.12
Ubiquitin thioesterase
UCH-L3
EC 3.4.19.12
Ubiquitin thioesterase L3
RefSeqNP_012633.1 (Protein)
NM_001181757.1 (DNA/RNA sequence)
NP_001257881.1 (Protein)
NM_001270952.1 (DNA/RNA sequence)
NP_005993.1 (Protein)
NM_006002.4 (DNA/RNA sequence)
MEROPSC12.002 (Cysteine)
C12.003 (Cysteine)
PfamPF01088 (Peptidase_C12)
[Graphical view]
PF01088 (Peptidase_C12)
[Graphical view]


UniProtKB:Accession NumberP35127P15374
Entry nameUBL1_YEASTUCHL3_HUMAN
ActivityThiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C- terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C- terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
Subunit

Subcellular location
Cytoplasm.
Cofactor


Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC04090C03635C00001C00496C00145C02188I00153I00154I00155
E.C.3.1.2.153.4.19.123.1.2.15,3.4.19.123.1.2.15,3.4.19.123.1.2.153.4.19.123.4.19.123.4.19.123.4.19.12
CompoundUbiquitin C-terminal thiolesterProtein N-ubiquityllysineH2OUbiquitinThiolProtein lysinePeptidyl-Cys-tetrahedral-intermediate (with previous peptide)Acyl-enzyme(Peptidyl-Cys-acyl group)Peptidyl-Cys-tetrahedral-intermediate
Typecarbohydrate,peptide/protein,sulfide groupamide group,lipid,peptide/proteinH2Opeptide/proteinsulfhydryl groupamine group,lipid,peptide/protein


ChEBI

15377






PubChem

22247451
962






                 
1cmxAUnboundUnbound UnboundUnboundUnboundUnboundIntermediate-analogue:GLZ 376(chain B)Unbound
1cmxCUnboundUnbound UnboundUnboundUnboundUnboundIntermediate-analogue:GLZ 776(chain D)Unbound
1uchAUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnbound
1xd3AUnboundUnbound UnboundUnboundUnboundTransition-state-analogue:GVEUnboundUnbound
1xd3CUnboundUnbound UnboundUnboundUnboundTransition-state-analogue:GVEUnboundUnbound

Active-site residues
resource
Swiss-prot;P15374 & literature [4], [8]
pdbCatalytic residuesMain-chain involved in catalysis
          
1cmxAGLN  84;CYS  90;HIS 166;ASP 181
CYS  90
1cmxCGLN 484;CYS 490;HIS 566;ASP 581
CYS 490
1uchAGLN  89;CYS  95;HIS 169;ASP 184
CYS  95
1xd3AGLN  89;CYS  95;HIS 169;ASP 184
CYS  95
1xd3CGLN  89;CYS  95;HIS 169;ASP 184
CYS  95

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]FIG 1, p.487-499
[4]p.3789-3791
[8]Fig.3, p.3878

references
[1]
PubMed ID2532544
JournalBiochemistry
Year1989
Volume28
Pages8530-6
AuthorsDuerksen-Hughes PJ, Williamson MM, Wilkinson KD
TitleAffinity chromatography using protein immobilized via arginine residues: purification of ubiquitin carboxyl-terminal hydrolases.
[2]
PubMed ID7845227
JournalMethods Enzymol
Year1994
Volume244
Pages486-500
AuthorsStorer AC, Menard R
TitleCatalytic mechanism in papain family of cysteine peptidases.
[3]
PubMed ID8639624
JournalBiochemistry
Year1996
Volume35
Pages6735-44
AuthorsLarsen CN, Price JS, Wilkinson KD
TitleSubstrate binding and catalysis by ubiquitin C-terminal hydrolases: identification of two active site residues.
[4]
CommentsX-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
PubMed ID9233788
JournalEMBO J
Year1997
Volume16
Pages3787-96
AuthorsJohnston SC, Larsen CN, Cook WJ, Wilkinson KD, Hill CP
TitleCrystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution.
Related PDB1uch
Related UniProtKBP15374
[5]
PubMed ID9485312
JournalBiochemistry
Year1998
Volume37
Pages1868-79
AuthorsDang LC, Melandri FD, Stein RL
TitleKinetic and mechanistic studies on the hydrolysis of ubiquitin C-terminal 7-amido-4-methylcoumarin by deubiquitinating enzymes.
[6]
PubMed ID10413498
JournalBiochemistry
Year1999
Volume38
Pages9242-53
AuthorsRajesh S, Sakamoto T, Iwamoto-Sugai M, Shibata T, Kohno T, Ito Y
TitleUbiquitin binding interface mapping on yeast ubiquitin hydrolase by NMR chemical shift perturbation.
[7]
PubMed ID10512618
JournalBiochemistry
Year1999
Volume38
Pages11634-42
AuthorsSakamoto T, Tanaka T, Ito Y, Rajesh S, Iwamoto-Sugai M, Kodera Y, Tsuchida N, Shibata T, Kohno T
TitleAn NMR analysis of ubiquitin recognition by yeast ubiquitin hydrolase: evidence for novel substrate recognition by a cysteine protease.
[8]
CommentsX-ray crystallography
PubMed ID10406793
JournalEMBO J
Year1999
Volume18
Pages3877-87
AuthorsJohnston SC, Riddle SM, Cohen RE, Hill CP
TitleStructural basis for the specificity of ubiquitin C-terminal hydrolases.
Related PDB1cmx
Related UniProtKBP35127
[9]
PubMed ID10518943
JournalJ Mol Biol
Year1999
Volume291
Pages1067-77
AuthorsWilkinson KD, Laleli-Sahin E, Urbauer J, Larsen CN, Shih GH, Haas AL, Walsh ST, Wand AJ
TitleThe binding site for UCH-L3 on ubiquitin: mutagenesis and NMR studies on the complex between ubiquitin and UCH-L3.
[10]
PubMed ID10893261
JournalJ Cell Biol
Year2000
Volume150
Pages119-30
AuthorsHolzl H, Kapelari B, Kellermann J, Seemuller E, Sumegi M, Udvardy A, Medalia O, Sperling J, Muller SA, Engel A, Baumeister W
TitleThe regulatory complex of Drosophila melanogaster 26S proteasomes. Subunit composition and localization of a deubiquitylating enzyme.
[11]
PubMed ID11390388
JournalJ Biol Chem
Year2001
Volume276
Pages30366-73
AuthorsMullally JE, Moos PJ, Edes K, Fitzpatrick FA
TitleCyclopentenone prostaglandins of the J series inhibit the ubiquitin isopeptidase activity of the proteasome pathway.
[12]
PubMed ID12705903
JournalBiochem Biophys Res Commun
Year2003
Volume304
Pages176-83
AuthorsNishikawa K, Li H, Kawamura R, Osaka H, Wang YL, Hara Y, Hirokawa T, Manago Y, Amano T, Noda M, Aoki S, Wada K
TitleAlterations of structure and hydrolase activity of parkinsonism-associated human ubiquitin carboxyl-terminal hydrolase L1 variants.
[13]
PubMed ID15571815
JournalBiochim Biophys Acta
Year2004
Volume1695
Pages189-207
AuthorsAmerik AY, Hochstrasser M
TitleMechanism and function of deubiquitinating enzymes.
[14]
CommentsX-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) IN COMPLEX WITH UBIQUITIN VINYLMETHYLESTER, AND ENZYMATIC ACTIVITY.
PubMed ID15531586
JournalJ Biol Chem
Year2005
Volume280
Pages1512-20
AuthorsMisaghi S, Galardy PJ, Meester WJ, Ovaa H, Ploegh HL, Gaudet R
TitleStructure of the ubiquitin hydrolase UCH-L3 complexed with a suicide substrate.
Related PDB1xd3
Related UniProtKBP15374

comments
This enzyme belongs to the peptidase family-C12.
According to the literature & Swissprot data, this enzyme catalyzes hydrolyses of amide bond (including peptide bond), thioester bond, and carboxlic ester bond.
According to the literature [4] & [8], this enzyme has got a catalytic triad composed of Cys/His/Asp and an oxyanion hole, made up by mainchain amide of the cysteine residue and sidechain amide of Gln.
The catalytic mechanism is also similar to other cysteine proteases, in which cysteine acts as a nucleophile, and histidine acts as a general acid-base.

createdupdated
2005-07-222012-10-23
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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