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Information on EC 3.4.22.B74 - SENP6 peptidase and Organism(s) Homo sapiens and UniProt Accession Q9GZR1

for references in articles please use BRENDA:EC3.4.22.B74
preliminary BRENDA-supplied EC number
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EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.22 Cysteine endopeptidases
                3.4.22.B74 SENP6 peptidase
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This record set is specific for:
Homo sapiens
UNIPROT: Q9GZR1
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
The enzyme catalyzes two essential functions in the SUMO pathway: processing of full-length SUMO-1, SUMO-2 and SUMO-3 to their mature forms and deconjugation of SUMO1, SUMO2 and SUMO3 from targeted proteins. Cleavage of Gly97-/-His98 bond in the SUMO-1 precursor with release of the propeptide His-Ser-Thr-Val. Cleavage of Gly93-/-Val94 bond in the SUMO-2 precursor with release of the propeptide Val94-Thyr. Cleavage of the Gly92-/-Val93 in the SUMO-3 precursor with release of the propeptide Pro-Glu-Ser-Ser-Leu-Ala-Gly-His-Ser-Phe. The enzyme catalyzes the desumoylation of SUMO-modified promyelocytic leukemia protein. SENP6 prefers the LRGG-/- sequence versus the QTGG-/- sequence. SENP6 is essential for inner kinetochore assembly.
Synonyms
susp1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(SUMO-1)-beta-galactosidase conjugate + H2O
SUMO-1 + beta-galactosidase
show the reaction diagram
SUSP1 expressed in Escherichia coli cells efficiently releases SUMO-1 from SUMO-1-beta-galactosidase fusion but not from other ubiquitin-like protein fusions, including Smt3-beta-galactosidase
-
-
?
(SUMO-3)-Ran GTPase-activating protein 1 conjugate + H2O
SUMO-3 + Ran GTPase-activating protein 1
show the reaction diagram
SENP6 and SENP7 prefer SUMO2 or SUMO3 in deconjugation reactions with rates comparable with those catalyzed by SENP2. In contrast to SENP2, SENP6 and SENP7 are less able to deconjugate SUMO1-RanGAP1, and products are only detected at enzyme concentrations 100 x higher than that observed for reactions containing SENP2
-
-
?
di-SUMO-2 + H2O
2 SUMO-2
show the reaction diagram
-
-
-
?
di-SUMO-3 + H2O
2 SUMO-3
show the reaction diagram
-
-
-
?
poly-SUMO-2 + H2O
?
show the reaction diagram
-
-
-
?
poly-SUMO-3 + H2O
?
show the reaction diagram
-
-
-
?
SUMO-1 precursor + H2O
SUMO-1 + His-Ser-Thr-Val
show the reaction diagram
SUMO-2 precursor + H2O
SUMO-2 + Val-Tyr
show the reaction diagram
SENP6 exhibits lower rates for processing pre-SUMO-1, pre-SUMO-2, or pre-SUMO3 in comparison with SENP2
-
-
?
SUMO-3 precursor + H2O
SUMO-3 + Val-Pro-Glu-Ser-Ser-Leu-Ala-Gly-His-Ser-Phe
show the reaction diagram
SENP6 exhibits lower rates for processing pre-SUMO-1, pre-SUMO-2, or pre-SUMO-3 in comparison with SENP2
-
-
?
SUMO-modified promyelocytic leukemia protein + H2O
SUMO + promyelocytic leukemia protein
show the reaction diagram
-
-
-
?
acetyl-LRGG-7-amido-4-trifluoromethylcoumarin + H2O
acetyl-LRGG + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
SENP6 prefers the LRGG sequence, residues typical of Nedd8 or ubiquitin in the P3 and P4 positions
-
-
?
acetyl-QTGG-7-amido-4-trifluoromethylcoumarin + H2O
acetyl-QTGG + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
very low activity
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
SUMO-modified promyelocytic leukemia protein + H2O
SUMO + promyelocytic leukemia protein
show the reaction diagram
-
-
-
?
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
truncated SUMO-2
-
whereas truncated SUMO-2 and -3 can substantially enhance SENP6 activity, neither truncated SUMO-1 nor truncated Nedd8 nor ubiquitin has this ability
-
truncated SUMO-3
-
whereas truncated SUMO-2 and -3 can substantially enhance SENP6 activity, neither truncated SUMO-1 nor truncated Nedd8 nor ubiquitin has this ability
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.8
assay at
8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
23
assay at
37
assay at
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
little activity
Manually annotated by BRENDA team
reproductive organs, such as testis, ovary, and prostate, contain much higher amounts of SUSP1 mRNA than colon and peripheral blood leukocyte
Manually annotated by BRENDA team
reproductive organs, such as testis, ovary, and prostate, contain much higher amounts of SUSP1 mRNA than colon and peripheral blood leukocyte
Manually annotated by BRENDA team
reproductive organs, such as testis, ovary, and prostate, contain much higher amounts of SUSP1 mRNA than colon and peripheral blood leukocyte
Manually annotated by BRENDA team
reproductive organs, such as testis, ovary, and prostate, contain much higher amounts of SUSP1 mRNA than colon and peripheral blood leukocyte
Manually annotated by BRENDA team
reproductive organs, such as testis, ovary, and prostate, contain much higher amounts of SUSP1 mRNA than colon and peripheral blood leukocyte
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
SUSP1 is exclusively localized to the cytoplasm of NIH3T3 and HeLa cells
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
depletion of SENP6 results in accumulation of endogenous SUMO-2/3 and SUMO-1 conjugates, and in accumulation of SUMO and promyelocytic leukemia protein in an increased number of promyelocytic leukemia nuclear bodies. Although SENP6 depletion drastically increases the size of promyelocytic leukemia nuclear bodies, the organizational structure of the body is not affected
evolution
-
the enzyme belongs to the SENP/ULP protease family
malfunction
-
cells lacking SENP6 show defects in spindle assembly and metaphase chromosome congression. A subset of proteins becomes undetectable on inner kinetochores after SENP6 depletion, particularly the CENP-H/I/K complex
physiological function
-
SENP6 is essential for inner kinetochore assembly. Balanced activities of SENP6 and RNF4 control vertebrate kinetochore assembly through SUMO-targeted destabilization of inner plate components
additional information
-
active site loop1 insertion is the determinant for the SUMO2/3 activity and specificity of SENP6, role of the SENP6/7-loop1 insertion in chain dismantling
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
SENP6_HUMAN
1112
0
126146
Swiss-Prot
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
126116
x * 126116, calculated from sequence
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 126116, calculated from sequence
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
expression in Escherichia coli
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Drag, M.; Mikolajczyk, J.; Krishnakumar, I.M.; Huang, Z.; Salvesen, G.S.
Activity profiling of human deSUMOylating enzymes (SENPs) with synthetic substrates suggests an unexpected specificity of two newly characterized members of the family
Biochem. J.
409
461-469
2008
Homo sapiens
Manually annotated by BRENDA team
Kim, K.I.; Baek, S.H.; Jeon, Y.J.; Nishimori, S.; Suzuki, T.; Uchida, S.; Shimbara, N.; Saitoh, H.; Tanaka, K.; Chung, C.H.
A new SUMO-1-specific protease, SUSP1, that is highly expressed in reproductive organs
J. Biol. Chem.
275
14102-14106
2000
Homo sapiens (Q9GZR1), Homo sapiens
Manually annotated by BRENDA team
Lima, C.D.; Reverter, D.
Structure of the human SENP7 catalytic domain and poly-SUMO deconjugation activities for SENP6 and SENP7
J. Biol. Chem.
283
32045-32055
2008
Homo sapiens (Q9GZR1)
Manually annotated by BRENDA team
Mukhopadhyay, D.; Arnaoutov, A.; Dasso, M.
The SUMO protease SENP6 is essential for inner kinetochore assembly
J. Cell Biol.
188
681-692
2010
Homo sapiens
Manually annotated by BRENDA team
Hattersley, N.; Shen, L.; Jaffray, E.G.; Hay, R.T.
The SUMO protease SENP6 is a direct regulator of PML nuclear bodies
Mol. Biol. Cell
22
78-90
2010
Homo sapiens (Q9GZR1)
Manually annotated by BRENDA team
Alegre, K.O.; Reverter, D.
Structural insights into the SENP6 loop1 structure in complex with SUMO2
Protein Sci.
23
433-441
2014
Homo sapiens
Manually annotated by BRENDA team