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Information on EC 3.4.22.B67 - Ulp2 peptidase and Organism(s) Saccharomyces cerevisiae and UniProt Accession P40537
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3.4.22.B67 Ulp2 peptidaseSpecify your search results
Word Map
- 3.4.22.B67
-
sumoylation
-
checkpoint
-
deconjugation
- sumo-1
-
sumo-protein
- helicase
-
sumo-specific
- hydroxyurea
-
restart
-
nuclear-localization
-
poly-sumo
-
dna-damaging
-
nucleolar
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ubiquitin-related
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spindle
-
euploidy
-
polysumoylation
The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Ulp2 hydrolyses the SUMO-SUMO linkage in poly-SUMO chains. It catalyzes desumoylation of SUMO-modified-Ndc10 kinetochore protein, SUMO-modified-Bir1 kinetochore protein or SUMO-modified-Cep3 kinetochore protein.
Synonyms
ulp2p, smt3-specific protease, ulp2 sumo protease, ulp2 sumo isopeptidase, sumo isopeptidase ulp2, sumo de-conjugating/chain-editing enzyme ulp2p, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
polySUMO-protein conjugate + H2O
SUMO + SUMO-SUMO + SUMO-SUMO-SUMO + truncated polySUMO-protein conjugate
Smt3-precursor + H2O
SMT3 + peptide
Ulp2 is able to process the Smt3 precursor in vivo, albeit inefficiently relative to Ulp1
-
-
?
tetra-SUMO + H2O
SUMO + ?
55% degradation within 60 min
-
-
?
SUMO-modified-Bir1 kinetochore protein + H2O
SUMO + Bir1 kinetochore protein
-
-
-
-
?
SUMO-modified-Cep3 kinetochore protein + H2O
SUMO + Cep3 kinetochore protein
-
-
-
-
?
SUMO-modified-Ndc10 kinetochore protein + H2O
SUMO + Ndc10 kinetochore protein
-
-
-
-
?
polySUMO-protein conjugate + H2O
SUMO + SUMO-SUMO + SUMO-SUMO-SUMO + truncated polySUMO-protein conjugate
-
-
-
?
polySUMO-protein conjugate + H2O
SUMO + SUMO-SUMO + SUMO-SUMO-SUMO + truncated polySUMO-protein conjugate
Ulp2 is capable of cleaving SUMO chains
-
-
?
polySUMO-protein conjugate + H2O
SUMO + truncated polySUMO-protein conjugate + H2O
Ulp2 can cleave the SUMO-SUMO linkage in poly-SUMO chains
-
-
?
polySUMO-protein conjugate + H2O
SUMO + truncated polySUMO-protein conjugate + H2O
Ulp2 can cleave the SUMO-SUMO linkage in poly-SUMO chains. The C-terminal noncatalytic domain of Ulp2 is required for efficient depolymerization of large poly-SUMO conjugates in vivo
-
-
?
Smt3-modified protein conjugate + H2O
Smt3 + protein
Ulp2 is able to cleave isopeptide-linked Smt3 molecules from natural substrates. Smt3-protein deconjugation by Ulp2 is important for normal meiotic development
-
-
?
Smt3-modified protein conjugate + H2O
Smt3 + protein
Ulp2 is able to cleave isopeptide-linked Smt3 molecules from natural substrates
-
-
?
additional information
?
-
Ulp2 SUMO protease is required for proper spindle dynamics during cell cycle resumption following a DNA damage-induced cell cycle arrest. It is proposed that one or more proteins is sumoylated following DNA damage-induced checkpoint activation, and this substrate(s) must be desumoylated by Ulp2 for proper cell cycle resumption
-
-
?
additional information
?
-
-
Ulp2 SUMO protease is required for proper spindle dynamics during cell cycle resumption following a DNA damage-induced cell cycle arrest. It is proposed that one or more proteins is sumoylated following DNA damage-induced checkpoint activation, and this substrate(s) must be desumoylated by Ulp2 for proper cell cycle resumption
-
-
?
additional information
?
-
isozyme Ulp2 is important for the control of poly-SUMO conjugates in cells and to dismantle SUMO chains in vitro. Isozyme Ulp2 acts sequentially rather than stochastically, processing substrate-linked poly-SUMO chains from their distal ends down to two linked SUMO moieties. Three linked SUMO units are the minimum length of a substrate-linked chain required for efficient binding to and processing by isozyme Ulp2, that disassembles SUMO chains by removing one SUMO moiety at a time from their ends, i.e. exo mechanism. Isozyme Ulp2 recognizes surfaces at or near the N-terminus of the distal SUMO moiety, as attachments to this end significantly reduce cleavage efficiency. Recombinant construction and expression of generate SMT3-led constructs, overview. Isozyme Ulp2 has three Smt3 binding sites that need to be occupied simultaneously to achieve full cooperative binding. Substrates equipped with mono- or di-Smt3, in contrast, are hardly bound if at all, substrate specificity analysis of immobilized recombinant enzyme, overview
-
-
?
additional information
?
-
-
Ulp2 is required for cell division following termination of the DNA damage checkpoint in Sacharomyces cerevisiae. The DNA damage checkpoint is a crucial defense mechanism used by cells to withstand DNA damage. Activation of the checkpoint halts the cell cycle at metaphase and allows time for DNA repair prior to cell division
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
polySUMO-protein conjugate + H2O
SUMO + SUMO-SUMO + SUMO-SUMO-SUMO + truncated polySUMO-protein conjugate
-
-
-
?
polySUMO-protein conjugate + H2O
SUMO + truncated polySUMO-protein conjugate + H2O
Ulp2 can cleave the SUMO-SUMO linkage in poly-SUMO chains
-
-
?
Smt3-modified protein conjugate + H2O
Smt3 + protein
Ulp2 is able to cleave isopeptide-linked Smt3 molecules from natural substrates. Smt3-protein deconjugation by Ulp2 is important for normal meiotic development
-
-
?
Smt3-precursor + H2O
SMT3 + peptide
Ulp2 is able to process the Smt3 precursor in vivo, albeit inefficiently relative to Ulp1
-
-
?
additional information
?
-
Ulp2 SUMO protease is required for proper spindle dynamics during cell cycle resumption following a DNA damage-induced cell cycle arrest. It is proposed that one or more proteins is sumoylated following DNA damage-induced checkpoint activation, and this substrate(s) must be desumoylated by Ulp2 for proper cell cycle resumption
-
-
?
additional information
?
-
-
Ulp2 SUMO protease is required for proper spindle dynamics during cell cycle resumption following a DNA damage-induced cell cycle arrest. It is proposed that one or more proteins is sumoylated following DNA damage-induced checkpoint activation, and this substrate(s) must be desumoylated by Ulp2 for proper cell cycle resumption
-
-
?
additional information
?
-
-
Ulp2 is required for cell division following termination of the DNA damage checkpoint in Sacharomyces cerevisiae. The DNA damage checkpoint is a crucial defense mechanism used by cells to withstand DNA damage. Activation of the checkpoint halts the cell cycle at metaphase and allows time for DNA repair prior to cell division
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
no inhibition by phenylmethylsulfonyl fluoride or the Dub-specific inhibitor ubiquitin aldehyde
-
additional information
-
no inhibition by phenylmethylsulfonyl fluoride or the Dub-specific inhibitor ubiquitin aldehyde
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
the N-terminal domain is essential for Ulp2 function and is required for nuclear targeting
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
-
disruption of Ulp2 causes a range of phenotypic defects, including temperature sensitivity, chromosome instability, and hypersensitivity to DNA and spindle damage. Ulp2-deleted cells died in the presence of DNA damage. In the presence of a DNA double-strand break, ulp2DELTA cells permanently arrested as large-budded cells regardless of whether the DNA DNA double-strand break is repairable or not
physiological function
malfunction
deletion of ULP2 promotes the accumulation of poly-SUMO chains and suppresses sgs1DELRA slx5D synthetic lethality and the slx5DELTA sporulation defect. It is speculated that the loss of ULP2 suppresses the toxicity of the sumoylated proteins that accumulate in slx5D-slx8D cells by permitting the extension of poly-SUMO chains on specific target proteins
malfunction
deletion of ULP2 results in a diverse set of aberrations, but the gene is not essential. In cells lacking Ulp2, specific Smt3-protein conjugates accumulate, and the conjugate pattern is distinct from that observed in a ulp1ts strain, which is defective for a distantly related Smt3-specific protease, Ulp1. The ulp2D mutant exhibits a pleiotropic phenotype that includes temperature-sensitive growth, abnormal cell morphology, decreased plasmid and chromosome stability, and a severe sporulation defect. The mutant is also hypersensitive to DNA damaging agents, hydroxyurea, and benomyl
malfunction
in yeast, mutants lacking Ulp2 accumulate high molecular weight SUMO-containing species only in the presence of wild-type Smt3. This is not the case in the smt3 mutants that do not have the critical lysine residues. Ulp2DELTA mutant strains are impaired in the mitotic-specific targeting of the condensin complex to chromatin, in particular rDNA chromatin. In addition, Ulp2 mutants display an increase in premature separation and fail to maintain cohesion at the regions proximal to centromere, which is caused in part by the poor regulation of the SUMO modification status of DNA Topoisomerase II
malfunction
inactivation of ULP2 in a strain expressing wild-type SUMO-activating enzyme results in slow and temperature-sensitive growth, and accumulation of SUMO conjugates
malfunction
spontaneous recombination is elevated in ulp2 strains. Ulp2 mutants display a reduced frequency of chromosome rearrangements. ulp2D mutants fail in chromosome segregation after exposure to methyl methanesulfonate
malfunction
ulp2DELTA mutants do not show persistent Rad53 phosphorylation following DNA damage, suggesting checkpoint signaling has been terminated and no longer asserts an arrest in these cells. Using Cdc14 localization as a cell cycle indicator, it is shown that nearly half of cells lacking Ulp2 can escape a checkpoint-induced metaphase arrest despite their inability to divide again. Moreover, half of permanently arrested ulp2DELTA cells show evidence of an aberrant mitotic spindle, suggesting that Ulp2 is required for proper spindle dynamics during cell cycle resumption following a DNA damage-induced cell cycle arrest
malfunction
a robust SUMO stress response occurs in response to 1 M sorbitol treatment of a ulp2 deletant strain
physiological function
role for Ulp2p in preventing the formation of DNA lesions that must be repaired through recombination. Ulp2p is also required to either suppress or resolve recombination-induced attachments between sister chromatids
physiological function
Ulp2 is a nuclear protein required for chromosome stability and cell cycle restart after checkpoint arrest
physiological function
Ulp2 is required for proper spindle dynamics during cell cycle resumption following a DNA damage-induced cell cycle arrest
physiological function
Ulp2 is required for the maintenance of chromosome structures. Ulp2 is specialized for chain editing activities
physiological function
Ulp2 prevents accumulation of SUMO chains in yeast
physiological function
isozyme Ulp2 controls the dynamic range of small ubiquitin-related modifiers, SUMO, chain lengths by trimming them from the distal ends
physiological function
the enzyme inhibits SUMO stress response consisting of consist of a simple SUMO conjugation-deconjugation cycle, overview. Isozyme Ulp2 is required to prevent the accumulation of SUMO chains in budding yeast
physiological function
the C-terminal regulatory domain of Ulp2 contains three distinct conserved motifs that control its in vivo substrate specificity and cell growth. Among them, a SUMO-interacting motif (SIM) coordinates with the domain of Ulp2 that binds to the nucleolar protein Csm1 to ensure maximal deSUMOylation of Ulp2's nucleolar substrates. The Csm1-binding domain of Ulp2 recruits this enzyme to the nucleolus, and Ulp2's C-terminal SIM promotes its SUMO protease activity and plays a key role in mediating the in vivo specificity of Ulp2
physiological function
-
Ulp2 is required for cell division following termination of the DNA damage checkpoint in Sacharomyces cerevisiae. The DNA damage checkpoint is a crucial defense mechanism used by cells to withstand DNA damage. Activation of the checkpoint halts the cell cycle at metaphase and allows time for DNA repair prior to cell division. Potentially, Ulp2 might be a part of the recovery and adaptation mechanisms but might act at a very late step to turn off the DNA damage-signaling cascade. An alternative, but not mutually exclusive, possibility is that Ulp2 acts after turnoff of the damage-signaling cascade to promote a step in cell division following release from the metaphase arrest. In either case, the role of Ulp2 most likely involves the desumoylation of one or more protein substrates, as we found that the SUMO protease activity of Ulp2 is required for its function and that inhibiting protein-SUMO conjugation could suppress the permanent arrest of ulp2DELTA cells after DNA damage
physiological function
-
cells lacking Ulp2 display a twofold increase in transcript levels across chromosome I (ChrI) and ChrXII. This is due to the two chromosomes being present at twice their normal copy number. Extra copies of ChrI and ChrXII appear quickly following loss of active Ulp2 and can be eliminated following reintroduction of Ulp2 gene. Increased dosage of two genes on ChrI-CLN3 and CCR4, encoding a G1-phase cyclin and a subunit of the Ccr4-Not deadenylase complex, respectively, suppresses Ulp2-dependent aneuploidy
physiological function
-
loss of Upl2 results in ChrI disomy, which is eliminated by extended passaging. The mRNA levels for almost all ribosomal proteins increase transiently upon initial loss of Ulp2, but elevated Ccr4 deadenylase levels limit excess ribosome formation. Extended passaging leads to increased levels of many small nucleolar RNAs involved in ribosome biogenesis, and higher dosage of three linked ChrXII small nucleolar RNA genes suppress ChrXII disomy in Ulp2 mutant cells
physiological function
-
Ulp2 is recruited to transcriptionally active genes to control local polysumoylation. Mutant Ulp2 cells show impaired association of RNA polymerase II with, and diminished expression of, constitutively active genes and the inducible CUP1 gene. Ulp2 loss sensitizes cells to 6-azauracil, a hallmark of transcriptional elongation defects
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C624A
site-directed mutagenesis, inactive isozyme Ulp2 mutant
H531A
catalytic-site mutant demonstrates permanent arrest after DNA damage similar to ulp2 deletion mutant
additional information
additional information
immobilization of isozyme Ulp2 via its C-terminal FLAG tag
additional information
a triple-Ala mutant of the SUMO-interacting motif SIM does not cause a noticeable growth defect. Contrary to wild-type, the mutant motif does not bind to tetra-SUMO or hexa-SUMO protein conjugates. The mutant significantly reduces Ulp2's SUMO protease activity for all of the linear SUMO substrates
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant FLAG-tagged and maltose-binding protein-fused isozyme Ulp2, containing a TEV protease recognition site, from Escherichia coli strain BL21 by amylose affinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
isozyme Ulp2, recombinant expression of GST-tagged isozyme Ulp2, expression of recombinant FLAG-tagged and maltose-binding protein-fused isozyme Ulp2, containing a TEV protease recognition site, in Escherichia coli strain BL21
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Schwartz, D.C.; Felberbaum, R.; Hochstrasser, M.
The Ulp2 SUMO protease is required for cell division following termination of the DNA damage checkpoint
Mol. Cell. Biol.
27
6948-6961
2007
Saccharomyces cerevisiae (P40537), Saccharomyces cerevisiae
Kim, J.H.; Baek, S.H.
Emerging roles of desumoylating enzymes
Biochim. Biophys. Acta
1792
155-162
2009
Saccharomyces cerevisiae (P40537)
Felberbaum, R.; Hochstrasser, M.
Ulp2 and the DNA damage response: desumoylation enables safe passage through mitosis
Cell Cycle
7
52-56
2007
Saccharomyces cerevisiae
Mullen, J.R.; Das, M.; Brill, S.J.
Genetic evidence that polysumoylation bypasses the need for a SUMO-targeted Ub ligase
Genetics
187
73-87
2011
Saccharomyces cerevisiae (P40537), Saccharomyces cerevisiae
Bylebyl, G.R.; Belichenko, I.; Johnson, E.S.
The SUMO isopeptidase Ulp2 prevents accumulation of SUMO chains in yeast
J. Biol. Chem.
278
44113-44120
2003
Saccharomyces cerevisiae (P40537), Saccharomyces cerevisiae
Kroetz, M.B.; Su, D.; Hochstrasser, M.
Essential role of nuclear localization for yeast Ulp2 SUMO protease function
Mol. Biol. Cell
20
2196-2206
2009
Saccharomyces cerevisiae (P40537), Saccharomyces cerevisiae
Li, S.J.; Hochstrasser, M.
The yeast ULP2 (SMT4) gene encodes a novel protease specific for the ubiquitin-like Smt3 protein
Mol. Cell. Biol.
20
2367-2377
2000
Saccharomyces cerevisiae (P40537), Saccharomyces cerevisiae
Schwienhorst, I.; Johnson, E.S.; Dohmen, R.J.
SUMO conjugation and deconjugation
Mol. Gen. Genet.
263
771-786
2000
Saccharomyces cerevisiae (P40537), Saccharomyces cerevisiae
Lee, M.T.; Bakir, A.A.; Nguyen, K.N.; Bachant, J.
The SUMO isopeptidase Ulp2p is required to prevent recombination-induced chromosome segregation lethality following DNA replication stress
PLoS Genet.
7
e1001355
2011
Saccharomyces cerevisiae (P40537), Saccharomyces cerevisiae
Eckhoff, J.; Dohmen, R.J.
In vitro studies reveal a sequential mode of chain processing by the yeast SUMO-specific protease Ulp2
J. Biol. Chem.
19
12268-12281
2015
Saccharomyces cerevisiae (P40537)
Lewicki, M.C.; Srikumar, T.; Johnson, E.; Raught, B.
The S. cerevisiae SUMO stress response is a conjugation-deconjugation cycle that targets the transcription machinery
J. Proteomics
118
39-48
2015
Saccharomyces cerevisiae (P40537), Saccharomyces cerevisiae BY4741/2 (P40537)
Ryu, H.Y.; Su, D.; Wilson-Eisele, N.R.; Zhao, D.; Lopez-Giraldez, F.; Hochstrasser, M.
The Ulp2 SUMO protease promotes transcription elongation through regulation of histone sumoylation
EMBO J.
38
e102003
2019
Saccharomyces cerevisiae
Ryu, H.Y.; Wilson, N.R.; Mehta, S.; Hwang, S.S.; Hochstrasser, M.
Loss of the SUMO protease Ulp2 triggers a specific multichromosome aneuploidy
Genes Dev.
30
1881-1894
2016
Saccharomyces cerevisiae
de Albuquerque, C.P.; Suhandynata, R.T.; Carlson, C.R.; Yuan, W.T.; Zhou, H.
Binding to small ubiquitin-like modifier and the nucleolar protein Csm1 regulates substrate specificity of the Ulp2 protease
J. Biol. Chem.
293
12105-12119
2018
Saccharomyces cerevisiae (P40537)
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