DB code: S00524

RLCP classification 1.14.30000.45 : Hydrolysis
1.13.30000.45 : Hydrolysis
1.12.30000.45 : Hydrolysis
CATH domain 3.40.532.10 : Ubiquitin C-terminal Hydrolase UCH-l3 Catalytic domain
E.C. 3.1.2.15 3.4.19.12
CSA 1uch 1cmx
M-CSA 1uch 1cmx
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P35127 Ubiquitin carboxyl-terminal hydrolase YUH1
UCH
EC 3.4.19.12
Ubiquitin thioesterase
NP_012633.1 (Protein)
NM_001181757.1 (DNA/RNA sequence)
C12.002 (Cysteine)
PF01088 (Peptidase_C12)
[Graphical View]
P15374 Ubiquitin carboxyl-terminal hydrolase isozyme L3
UCH-L3
EC 3.4.19.12
Ubiquitin thioesterase L3
NP_001257881.1 (Protein)
NM_001270952.1 (DNA/RNA sequence)
NP_005993.1 (Protein)
NM_006002.4 (DNA/RNA sequence)
C12.003 (Cysteine)
PF01088 (Peptidase_C12)
[Graphical View]

KEGG enzyme name
ubiquitin 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 )

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P15374 UCHL3_HUMAN 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). Cytoplasm.
P35127 UBL1_YEAST 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).

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C04090 C03635 C00001 C00496 C00145 C02188 I00153 I00154 I00155
E.C. 3.1.2.15
3.4.19.12
3.1.2.15
3.4.19.12
3.1.2.15
3.4.19.12
3.1.2.15
3.4.19.12
3.4.19.12
3.4.19.12
3.4.19.12
Compound Ubiquitin C-terminal thiolester Protein N-ubiquityllysine H2O Ubiquitin Thiol Protein lysine Peptidyl-Cys-tetrahedral-intermediate (with previous peptide) Acyl-enzyme(Peptidyl-Cys-acyl group) Peptidyl-Cys-tetrahedral-intermediate
Type carbohydrate,peptide/protein,sulfide group amide group,lipid,peptide/protein H2O peptide/protein sulfhydryl group amine group,lipid,peptide/protein
ChEBI 15377
PubChem 22247451
962
1cmxA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:GLZ_376(chain B) Unbound
1cmxC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:GLZ_776(chain D) Unbound
1uchA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1xd3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:GVE Unbound Unbound
1xd3C Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:GVE Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P15374 & literature [4], [8]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1cmxA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 84;CYS 90;HIS 166;ASP 181 CYS 90
1cmxC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 484;CYS 490;HIS 566;ASP 581 CYS 490
1uchA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 89;CYS 95;HIS 169;ASP 184 CYS 95
1xd3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 89;CYS 95;HIS 169;ASP 184 CYS 95
1xd3C Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 89;CYS 95;HIS 169;ASP 184 CYS 95

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
FIG 1, p.487-499
[4]
p.3789-3791
[8]
Fig.3, p.3878

References
[1]
Resource
Comments
Medline ID
PubMed ID 2532544
Journal Biochemistry
Year 1989
Volume 28
Pages 8530-6
Authors Duerksen-Hughes PJ, Williamson MM, Wilkinson KD
Title Affinity chromatography using protein immobilized via arginine residues: purification of ubiquitin carboxyl-terminal hydrolases.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7845227
Journal Methods Enzymol
Year 1994
Volume 244
Pages 486-500
Authors Storer AC, Menard R
Title Catalytic mechanism in papain family of cysteine peptidases.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8639624
Journal Biochemistry
Year 1996
Volume 35
Pages 6735-44
Authors Larsen CN, Price JS, Wilkinson KD
Title Substrate binding and catalysis by ubiquitin C-terminal hydrolases: identification of two active site residues.
Related PDB
Related UniProtKB
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
Medline ID
PubMed ID 9233788
Journal EMBO J
Year 1997
Volume 16
Pages 3787-96
Authors Johnston SC, Larsen CN, Cook WJ, Wilkinson KD, Hill CP
Title Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution.
Related PDB 1uch
Related UniProtKB P15374
[5]
Resource
Comments
Medline ID
PubMed ID 9485312
Journal Biochemistry
Year 1998
Volume 37
Pages 1868-79
Authors Dang LC, Melandri FD, Stein RL
Title Kinetic and mechanistic studies on the hydrolysis of ubiquitin C-terminal 7-amido-4-methylcoumarin by deubiquitinating enzymes.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10413498
Journal Biochemistry
Year 1999
Volume 38
Pages 9242-53
Authors Rajesh S, Sakamoto T, Iwamoto-Sugai M, Shibata T, Kohno T, Ito Y
Title Ubiquitin binding interface mapping on yeast ubiquitin hydrolase by NMR chemical shift perturbation.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10512618
Journal Biochemistry
Year 1999
Volume 38
Pages 11634-42
Authors Sakamoto T, Tanaka T, Ito Y, Rajesh S, Iwamoto-Sugai M, Kodera Y, Tsuchida N, Shibata T, Kohno T
Title An NMR analysis of ubiquitin recognition by yeast ubiquitin hydrolase: evidence for novel substrate recognition by a cysteine protease.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10406793
Journal EMBO J
Year 1999
Volume 18
Pages 3877-87
Authors Johnston SC, Riddle SM, Cohen RE, Hill CP
Title Structural basis for the specificity of ubiquitin C-terminal hydrolases.
Related PDB 1cmx
Related UniProtKB P35127
[9]
Resource
Comments
Medline ID
PubMed ID 10518943
Journal J Mol Biol
Year 1999
Volume 291
Pages 1067-77
Authors Wilkinson KD, Laleli-Sahin E, Urbauer J, Larsen CN, Shih GH, Haas AL, Walsh ST, Wand AJ
Title The binding site for UCH-L3 on ubiquitin: mutagenesis and NMR studies on the complex between ubiquitin and UCH-L3.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 10893261
Journal J Cell Biol
Year 2000
Volume 150
Pages 119-30
Authors Holzl H, Kapelari B, Kellermann J, Seemuller E, Sumegi M, Udvardy A, Medalia O, Sperling J, Muller SA, Engel A, Baumeister W
Title The regulatory complex of Drosophila melanogaster 26S proteasomes. Subunit composition and localization of a deubiquitylating enzyme.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 11390388
Journal J Biol Chem
Year 2001
Volume 276
Pages 30366-73
Authors Mullally JE, Moos PJ, Edes K, Fitzpatrick FA
Title Cyclopentenone prostaglandins of the J series inhibit the ubiquitin isopeptidase activity of the proteasome pathway.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 12705903
Journal Biochem Biophys Res Commun
Year 2003
Volume 304
Pages 176-83
Authors Nishikawa K, Li H, Kawamura R, Osaka H, Wang YL, Hara Y, Hirokawa T, Manago Y, Amano T, Noda M, Aoki S, Wada K
Title Alterations of structure and hydrolase activity of parkinsonism-associated human ubiquitin carboxyl-terminal hydrolase L1 variants.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 15571815
Journal Biochim Biophys Acta
Year 2004
Volume 1695
Pages 189-207
Authors Amerik AY, Hochstrasser M
Title Mechanism and function of deubiquitinating enzymes.
Related PDB
Related UniProtKB
[14]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) IN COMPLEX WITH UBIQUITIN VINYLMETHYLESTER, AND ENZYMATIC ACTIVITY.
Medline ID
PubMed ID 15531586
Journal J Biol Chem
Year 2005
Volume 280
Pages 1512-20
Authors Misaghi S, Galardy PJ, Meester WJ, Ovaa H, Ploegh HL, Gaudet R
Title Structure of the ubiquitin hydrolase UCH-L3 complexed with a suicide substrate.
Related PDB 1xd3
Related UniProtKB P15374

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.

Created Updated
2005-07-22 2012-10-23