DB code: S00524

RLCP classification	1.12.30000.45 : Hydrolysis
	1.13.30000.45 : Hydrolysis
	1.14.30000.45 : 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	1cmx 1uch
M-CSA	1cmx 1uch
MACiE

CATH domain	Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	RefSeq	MEROPS	Pfam
P35127	Ubiquitin carboxyl-terminal hydrolase YUH1	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 )

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
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).
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.

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 15377
PubChem			22247451 962 22247451 962

1cmxA	Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Intermediate-analogue:GLZ_376(chain B)	Unbound
1cmxC	Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Intermediate-analogue:GLZ_776(chain D)	Unbound
1uchA	Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1xd3A	Unbound	Unbound		Unbound	Unbound	Unbound	Transition-state-analogue:GVE	Unbound	Unbound
1xd3C	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	GLN 84;CYS 90;HIS 166;ASP 181			CYS 90
1cmxC	GLN 484;CYS 490;HIS 566;ASP 581			CYS 490
1uchA	GLN 89;CYS 95;HIS 169;ASP 184			CYS 95
1xd3A	GLN 89;CYS 95;HIS 169;ASP 184			CYS 95
1xd3C	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.

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