3.4.19.12: ubiquitinyl hydrolase 1

This is an abbreviated version!
For detailed information about ubiquitinyl hydrolase 1, go to the full flat file.

Reaction

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) =

Synonyms

A20, AD-019, AMSH, associated molecule with the SH3-domain of STAM, AT-3, ataxin-3, BAP1, BPLF1, BRCA1-associated protein-1, C-terminal hydrolases UCHL3, C-terminal ubiquitin hydrolase, Cezanne, CGI-70, CYLD, de-ubiquitinating enzyme, deubiquinating isopeptidase T, deubiquitinating enzyme, Doa4, Doa4 ubiquitin hydrolase, Doa4p ubiquitin isopeptidase, DUB, dUCH, EC 3.1.2.15, esterase, ubiquitin thiol-, hydrolase, ubiquitin carboxyl-terminal, hydrolase, ubiquitin carboxyl-terminal (Aplysia californica gene Ap-uch), Iso-T, isopeptidase, isopeptidase T, More, Neuron cytoplasmic protein 9.5, neuronal-specific protein gene product 9.5, OsUCH1, OsUCH2, OsUCH3, OsUCH4, OsUCH5, OTU-1, OTUB1, OTUB2, Otubain-1, Otubain-2, ovarian tumour 1, PA-700 associated isopeptidase, papain-like protease, PGP 9.5, PGP 9.5/UCHL1, PGP9.5, PGP9.5.1, PLP2, PLpro, Ub isopeptidase, ubiquitin C terminal hydrolase 1, ubiquitin C-terminal hydrolase, ubiquitin C-terminal hydrolase (Aplysia californica gene Ap-uch), ubiquitin C-terminal hydrolase 1, ubiquitin C-terminal hydrolase 37, ubiquitin C-terminal hydrolase 8, ubiquitin C-terminal hydrolase isoform L3, ubiquitin C-terminal hydrolase L-1, ubiquitin C-terminal hydrolase L1, ubiquitin C-terminal hydrolase L3, Ubiquitin C-terminal hydrolase UCH37, ubiquitin C-terminal hydrolase-1, ubiquitin C-terminal hydrolase-L1, ubiquitin C-terminal hydrolase-L3, ubiquitin C-terminal hydrolase-L5, ubiquitin C-terminal hydrorase-L1, ubiquitin carboxy terminal hydrolase-L1, ubiquitin carboxy terminal hydrolase-L3, ubiquitin carboxy-terminal hydrolase, ubiquitin carboxy-terminal hydrolase 1, ubiquitin carboxy-terminal hydrolase L1, ubiquitin carboxy-terminal hydrolase-L1, ubiquitin carboxy-terminal hydrolase-L3, ubiquitin carboxyhydrolase L3, ubiquitin carboxyl terminal esterase L1, ubiquitin carboxyl terminal hydrolase 1, ubiquitin carboxyl terminal hydrolase L1, ubiquitin carboxyl terminal hydrolase-L1, ubiquitin carboxyl-terminal hydrolase, ubiquitin carboxyl-terminal hydrolase 1, ubiquitin carboxyl-terminal hydrolase 44, ubiquitin carboxyl-terminal hydrolase isozyme L1, ubiquitin carboxyl-terminal hydrolase L-1, ubiquitin carboxyl-terminal hydrolase L1, ubiquitin carboxyl-terminal hydrolase l3, ubiquitin carboxyl-terminal hydrolase L5, ubiquitin carboxyl-terminal hydrolase-L1, ubiquitin carboxyl-terminal hydrolase-L5, ubiquitin carboxyterminal hydrolase L1, ubiquitin carboxyterminal hydrolase L3, ubiquitin carboxyterminal hydrolase-L1, ubiquitin hydrolase, ubiquitin hydrolase Uch-L1, ubiquitin hydrolase UCH-L3, ubiquitin isopeptidase, Ubiquitin thiolesterase, Ubiquitin thiolesterase L1, Ubiquitin thiolesterase L3, Ubiquitin thiolesterase L4, Ubiquitin thiolesterase L5, ubiquitin-C-terminal hydrolase L1, ubiquitin-carboxyl-terminal hydrolase PGP-9.5, ubiquitin-specific protease 44, UBPY, UCH, UCH L-1, UCH L1, UCH-1, UCH-8, UCH-L1, UCH-L2, UCH-L3, UCH-L4, UCH-L5, UCH37, UCH54, UCHL-1, UCHL-3, UCHL1, UCHL1/PGP 9.5, UCHL2, Uchl3, UCHL5, UCHL5N240, USP19, USP22, USP44, yeast ubiquitin hydrolase, YUH, YUH1

ECTree

     3 Hydrolases

         3.4 Acting on peptide bonds (peptidases)

             3.4.19 Omega peptidases

                3.4.19.12 ubiquitinyl hydrolase 1

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Results	in table
34	Activating Compound
102795	AA Sequence
56	Application
2	CAS Registry Number
64	Cloned(Commentary)
8	Crystallization (Commentary)
8472	Disease/ Diagnostics
18	Expression
94	General Information
2	General Stability
54	IC50 Value
161	Inhibitors
8	kcat/KM [mM/s]
31	Ki Value [mM]
63	KM Value [mM]
74	Localization
15	Metals/Ions
33	Molecular Weight [Da]
85	Natural Substrates/ Products (Substrates)
386	Organism
4	Oxidation Stability
825	PDB ID
29	pH Optimum
3	pH Range
3	pI Value
5	Posttranslational Modification
151	Protein Variants
41	Purification (Commentary)
3	Reaction
1	Reaction Type
218	Reference
1	Renatured (Commentary)
454	Source Tissue
18	Specific Activity [micromol/min/mg]
3	Storage Stability
284	Substrates and Products (Substrate)
32	Subunits
468	Synonyms
21	Temperature Optimum [°C]
1	Temperature Range [°C]
4	Temperature Stability [°C]
49	Turnover Number [1/s]

Activating Compound

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Activating Compound on EC 3.4.19.12 - ubiquitinyl hydrolase 1

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ACTIVATING COMPOUND

ORGANISM

UNIPROT

COMMENTARY

LITERATURE

IMAGE

2-mercaptoethanol

4 entries

4-hydroxy-2-alkenal

Homo sapiens

-

modification of UCH-L1 promotes direct interactions between UCH-L1 and tubulin

680081

4-hydroxy-2-nonenal

Homo sapiens

-

modification of UCH-L1 promotes direct interactions between UCH-L1 and tubulin

680081

Adrm1

Homo sapiens

Q9Y5K5

recruits Uch37 to the proteasome. Binds the carboxy-terminal tail of Uch37. Following binding, Adrm1 relieves Uch37 autoinhibition, accelerating the hydrolysis of ubiquitin-7-amido-4-methylcoumarin

682066

-

DTT

6 entries

ethyl 1-[N-(4-methylphenyl)-N-(methylsulfonyl)alanyl]-4-piperidinecarboxylate

Homo sapiens

P09936

-

710080

H2O2

Homo sapiens

P09936

-

682794

poly-L-Arg

Gallus gallus

-

activation

36452

poly-L-Lys

Gallus gallus

-

activation

36452

Sodium citrate

3 entries

TNFalpha

Homo sapiens

-

inducer

698869

-

tumor necrosis factor-alpha

Homo sapiens

-

treatment of cultured vascular smooth muscle cells for 24 and 48 hours does not significantly alter UCHL1 mRNA levels, whereas long term treatment (96 hours) significantly increases UCHL1 mRNA levels. Treatment of aortic endothelial cells and aortic smooth muscle cells with tumor necrosis factor-alpha for 24 hours does not significantly alter UCHL1 mRNA levels

677876

-

ubiquitin

3 entries

additional information

12 entries

-

2-mercaptoethanol

Bos taurus

-

active-site thiol is very sensitive to oxidation and requires reductants

35003

2-mercaptoethanol

Drosophila melanogaster

-

active-site thiol is very sensitive to oxidation and requires reductants

35003

2-mercaptoethanol

Homo sapiens

-

active-site thiol is very sensitive to oxidation and requires reductants

35003

2-mercaptoethanol

Rattus norvegicus

-

active-site thiol is very sensitive to oxidation and requires reductants

35003

DTT

Bos taurus

-

active-site thiol is very sensitive to oxidation and requires reductants

35003

DTT

Bos taurus

-

inactivated in absence of DTT

36451

DTT

Drosophila melanogaster

-

active-site thiol is very sensitive to oxidation and requires reductants

35003

DTT

Homo sapiens

-

active-site thiol is very sensitive to oxidation and requires reductants

35003

DTT

Mus musculus

-

required, hydrolase activity of UCH-L1 in vitro is decreased when reducing dithiothreitol is omitted from the reaction buffer

710082

DTT

Rattus norvegicus

-

active-site thiol is very sensitive to oxidation and requires reductants

35003

Sodium citrate

Homo sapiens

P15374, P45974, Q5VVQ6

activation of the enzymes with increasing salt concentration, reaching a maximum above 0.8 M. Most effective activation in the case of UCH-L3, where 1.1 M sodium citrate enhances catalysis on the synthetic substrate Ac-LRGG-7-amido-4-trifluoromethylcoumarin about 24fold, compared with low-salt conditions. The tetrapeptide substrate Ac-LRGG-7-amido-4-trifluoromethylcoumarin and the pentapeptide substrate containing alanine at position P5, namely Ac-ALRGG-7-amido-4-trifluoromethylcoumarin, both demonstrate a salt effect, but the pentapeptide substrate containing arginine in position P5, Ac-RLRGG-7-amido-4-trifluoromethylcoumarin, does not demonstrate one

696098

Sodium citrate

Homo sapiens

P15374, P45974, Q5VVQ6

activation of the enzymes with increasing salt concentration, reaching a maximum above 0.8 M. The tetrapeptide substrate Ac-LRGG-7-amido-4-trifluoromethylcoumarin and the pentapeptide substrate containing alanine at position P5, namely Ac-ALRGG-7-amido-4-trifluoromethylcoumarin, both demonstrate a salt effect, but the pentapeptide substrate containing arginine in position P5, Ac-RLRGG-7-amido-4-trifluoromethylcoumarin, does not demonstrate one

696098

Sodium citrate

Homo sapiens

P15374, P45974, Q5VVQ6

activation of the enzymes with increasing salt concentration, reaching a maximum above 0.8 M. Weakest activation in the case of IsoT, where there is almost no increase in catalysis compared with low salt conditions. The tetrapeptide substrate Ac-LRGG-7-amido-4-trifluoromethylcoumarin and the pentapeptide substrate containing alanine at position P5, namely Ac-ALRGG-7-amido-4-trifluoromethylcoumarin, both demonstrate a salt effect, but the pentapeptide substrate containing arginine in position P5, Ac-RLRGG-7-amido-4-trifluoromethylcoumarin, does not demonstrate one

696098

ubiquitin

Homo sapiens

P15374, P45974, Q5VVQ6

20fold enhancement of the cleavage of Ac-LRGG-7-amido-4-trifluoromethylcoumarin by IsoT in the presence of equimolar ubiquitin

696098

ubiquitin

Homo sapiens

P15374, P45974, Q5VVQ6

iIn the case of OTU-1 full-length ubiquitin does not result in any substantial decrease or increase of the processing of the fluorigenic substrate

696098

ubiquitin

Oryctolagus cuniculus

-

submicromolar concentrations activate while higher concentrations inhibit the enzyme, regulatory function, binding via 2 ubiquitin binding sites extending the active site

646099

additional information

Homo sapiens

P15374

enzyme activation modeling

666752

-

additional information

Homo sapiens

-

enzyme activation modeling

666752

-

additional information

Homo sapiens

P09936

6-hydroxydopamine induces oxidative stress in human neuroblastoma SH-SY5Y cells. UCH-L1 is an oxidative-stress-reporting biomarker

681102

-

additional information

Homo sapiens

P15374

enzymatic activation mediated by substrate binding

666752

-

additional information

Homo sapiens

-

enzymatic activation mediated by substrate binding

666752

-

additional information

Homo sapiens

-

treatment of aortic endothelial cells and aortic smooth muscle cells with human recombinant epidermal growth factor, fibroblast growth factor-2, vascular endothelial growth factor, lipopolysaccharide, angiotensin II or hydrogen peroxide for 24 hours does not significantly alter UCHL1 mRNA levels

677876

-

additional information

Homo sapiens

P09936

UCH-L1 expression correlates with podocyte ubiquitin content and internalization of the podocyte-specific proteins nephrin and alpha-actinin-4

699730

-

additional information

Homo sapiens

-

UCH-L1 expression correlates with podocyte ubiquitin content and internalization of the podocyte-specific proteins nephrin and alpha-actinin-4

699730

-

additional information

Mus musculus

-

UCH-L1 is easily affected by redox status

710082

-

additional information

Rattus norvegicus

-

UCH-L1 activity is regulated by synaptic activity. Stimulation of synaptic activity by NMDA/glycine significantly up-regulates UCH-L1 activity in cultured neurons. NMDA-induced up-regulation of UCH-L1 activity is efficiently blocked by pre-treatment of neurons with the NMDA receptor antagonist D-2-amino-5-phosphonopentanoic acid

709638

-

additional information

Rattus norvegicus

-

UCH-L1 is significantly elevated in cerebrospinal fluid following controlled cortical impact and middle cerebral artery occlusion, as a model of ischemic stroke, in rats, overview

708390

-

additional information

Severe acute respiratory syndrome-related coronavirus

-

activation of the enzyme with increasing salt concentration, reaching a maximum above 0.8 M

696098

-