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Information on EC 2.7.11.21 - polo kinase and Organism(s) Saccharomyces cerevisiae and UniProt Accession P32562
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2.7.11.21 polo kinaseIUBMB Comments
The enzyme associates with the spindle pole during mitosis and is thought to play an important role in the dynamic function of the mitotic spindle during chromosome segregation. The human form of the enzyme, Plk1, does not phosphorylate histone H1, enolase and phosvitin but it can phosphorylate myelin basic protein and microtubule-associated protein MAP-2, although to a lesser extent than casein .
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Word Map
- 2.7.11.21
-
mitotic
- centrosome
-
checkpoint
-
cytokinesis
-
aurora
- microtubule
-
anaphase
- sirnas
-
polo-box
- cyclin
- kinetochore
-
cyclin-dependent
-
exit
- centriole
-
interphase
-
chromatid
-
metaphase
-
cell-cycle
-
meiosis
-
m-phase
-
faithful
-
aneuploidy
-
anaphase-promoting
-
pericentriolar
-
prometaphase
- cohesins
-
prophase
-
centromeres
- cdc25c
-
midbody
-
mitosis-specific
-
atp-competitive
- bubr1
-
kinetochore-microtubule
-
misalign
- midzone
- diagnostics
- pharmacology
-
missegregation
-
microtubule-organizing
-
monopolar
- securin
- wee1
- drug development
- cdc14
- analysis
-
condensin
-
metaphase-anaphase
- medicine
- gamma-tubulin
-
furrow
- mps1
- separase
- chk1
-
telophase
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
+
a [protein]-(L-serine/L-threonine)
=
+
a [protein]-(L-serine/L-threonine) phosphate
Synonyms
polo-like kinase 1, polo-like kinase, plk-1, polo kinase, polo-like kinase 4, polo-like kinase-1, tbplk, plk1 kinase, cdc5p, polo-like kinase 2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Cdc5
-
-
FGF-inducible kinase
-
-
-
-
polo-like kinase
-
-
Proliferation-related kinase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (spindle-pole-dependent)
The enzyme associates with the spindle pole during mitosis and is thought to play an important role in the dynamic function of the mitotic spindle during chromosome segregation. The human form of the enzyme, Plk1, does not phosphorylate histone H1, enolase and phosvitin but it can phosphorylate myelin basic protein and microtubule-associated protein MAP-2, although to a lesser extent than casein [2].
CAS REGISTRY NUMBER
COMMENTARY
149433-93-2
Polo kinase
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
ATP + Mus81-Mms4 resolvase
ADP + phosphorylated Mus81-Mms4 resolvase
-
-
-
?
ATP + Nud1
ADP + phosphorylated Nud1
Cdc5 and Cdc28 activities are required for proper phosphorylation of Nud1
-
-
?
ATP + Slk19
ADP + phosphorylated Slk19
Cdc5 and Cdc28 activities are required for proper phosphorylation of Slk19
-
-
?
ATP + Stu2
ADP + phosphorylated Stu2
Cdc5 and Cdc28 activities are required for proper phosphorylation of Stu2
-
-
?
ATP + Bem3
ADP + phosphorylated Bem3
-
bound by the polo-box domain of Cdc5
-
-
?
ATP + bovine serum albumin
ADP + phosphorylated bovine serum albumin
-
very weak phosphorylation
-
-
?
ATP + Ecm25
ADP + phosphorylated Ecm25
-
bound by the polo-box domain of Cdc5
-
-
?
ATP + Fkh2p
ADP + phosphorylated Fkh2p
-
Fkh2p is only poorly phosphorylated by Cdc5p, Fkh2p has a function in nucleating the formation of a Fkh2p-Ndd1p-Cdc5p complex on CLB2 cluster promoters, and the subsequent Cdc5p-dependent phosphorylation of Ndd1p at Ser 85
-
-
?
ATP + histone H1
ADP + phosphorylated histone H1
-
substrate used in kinase assay
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
very weak phosphorylation
-
-
?
ATP + Ndd1p
ADP + phosphorylated Ndd1p
-
phosphorylation of Ser 85, phosphorylation is required for the normal temporal expression of cell-cycle-regulated genes such as CLB2 and SWI5 in G2/M phase
-
-
?
ATP + Rom2
ADP + phosphorylated Rom2
-
bound by the polo-box domain of Cdc5
-
-
?
ATP + Sac7
ADP + phosphorylated Sac7
-
bound by the polo-box domain of Cdc5
-
-
?
ATP + Tus1
ADP + phosphorylated Tus1
-
bound by the polo-box domain of Cdc5
-
-
?
ATP + casein
ADP + phosphorylated casein
-
best in vitro substrate
-
-
?
ATP + cohesin
ADP + phosphorylated cohesin
-
phosphorylation by Cdc5 required for removal of cohesin from chromosomes
-
-
?
ATP + cohesin
ADP + phosphorylated cohesin
-
phosphorylation adjacent to the cleavage site of Scc1 by Cdc5
-
-
?
ATP + Mad3
ADP + phosphorylated Mad3
-
phosphorylation of Mad3 isozymes at 5 serine residues, S222, S380, S466, S504, and especially at S268, during spindle checkpoint activation, Mad3 is an inhibitor of Cdc20/APC ubiquitin ligase, overview
-
-
?
ATP + Mad3
ADP + phosphorylated Mad3
-
recombinant HA-tagged wild-type and mutant Mad3 substrate proteins, the activity with mutants in which phorylation site Ser is replaced by Ala is highly reduced, Mad3 is a homologue to the human BubR1 protein
-
-
?
additional information
?
-
required for the initiation of chromosomal DNA replication in Saccharomyces cerevisiae and interaction with the CDC7 protein kinase
-
-
?
additional information
?
-
-
Cdc5 plays a role in chromosomes segregation during meiosis I, it is required for phosphorylation and removal of cohesin from chromosomes, it is required for sister-kinetochore orientation with associated Mam1 protein, mechanism, overview
-
-
?
additional information
?
-
-
Plk1 is important in activation and regulation of spindle assembly during mitosis
-
-
?
additional information
?
-
-
polo kinase Cdc5 is involved as part of the FEAR network, i.e. fourteen early anaphase release network, and of MEN network, i.e. mitotic exit network, in controlling protein phosphatase Cdc14 localization and activity, the enzyme induces phosphorylation of Cdc14 and Cfi1/Net1 by activating the networks, overview
-
-
?
additional information
?
-
-
the enzyme is pivotal in cell division as a regulator of cell cycle checkpoints in mitotic progression, Cdc5 is part of mitotic networks, e.g. the fourteen early anaphase release network FEAR for Cdc14 release, overview
-
-
?
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
ATP + Mus81-Mms4 resolvase
ADP + phosphorylated Mus81-Mms4 resolvase
-
-
-
?
ATP + cohesin
ADP + phosphorylated cohesin
-
phosphorylation by Cdc5 required for removal of cohesin from chromosomes
-
-
?
ATP + Mad3
ADP + phosphorylated Mad3
-
phosphorylation of Mad3 isozymes at 5 serine residues, S222, S380, S466, S504, and especially at S268, during spindle checkpoint activation, Mad3 is an inhibitor of Cdc20/APC ubiquitin ligase, overview
-
-
?
ATP + Rom2
ADP + phosphorylated Rom2
-
bound by the polo-box domain of Cdc5
-
-
?
ATP + Tus1
ADP + phosphorylated Tus1
-
bound by the polo-box domain of Cdc5
-
-
?
additional information
?
-
required for the initiation of chromosomal DNA replication in Saccharomyces cerevisiae and interaction with the CDC7 protein kinase
-
-
?
additional information
?
-
-
Cdc5 plays a role in chromosomes segregation during meiosis I, it is required for phosphorylation and removal of cohesin from chromosomes, it is required for sister-kinetochore orientation with associated Mam1 protein, mechanism, overview
-
-
?
additional information
?
-
-
Plk1 is important in activation and regulation of spindle assembly during mitosis
-
-
?
additional information
?
-
-
polo kinase Cdc5 is involved as part of the FEAR network, i.e. fourteen early anaphase release network, and of MEN network, i.e. mitotic exit network, in controlling protein phosphatase Cdc14 localization and activity, the enzyme induces phosphorylation of Cdc14 and Cfi1/Net1 by activating the networks, overview
-
-
?
additional information
?
-
-
the enzyme is pivotal in cell division as a regulator of cell cycle checkpoints in mitotic progression, Cdc5 is part of mitotic networks, e.g. the fourteen early anaphase release network FEAR for Cdc14 release, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
-
20 mM Mg2+ enhances the enzyme activity, 10 mM is used in assay conditions
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Mn2+
-
10 mM Ca2+ inhibits the enzyme activity, 5 mM is used in assay conditions
additional information
-
the enzyme activity is inhibited upon DNA damage
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
Cdc5 is activated by Cdk1 phosphorylation
-
additional information
-
Cdc5 is activated by Cdk1 phosphorylation
-
additional information
phosphorylation of threonine residues in the T-loop of the kinase domain is pivotal for PLKs activation
-
additional information
-
phosphorylation of threonine residues in the T-loop of the kinase domain is pivotal for PLKs activation
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
additional information
mutants Cdc5-T238A and Cdc5-ad variants, as well as the wild-type protein, were detectable in late S and G2/M phases, but not in late G1 and early S, mirroring the expression of the CDK1-cyclin Clb2
additional information
-
mutants Cdc5-T238A and Cdc5-ad variants, as well as the wild-type protein, were detectable in late S and G2/M phases, but not in late G1 and early S, mirroring the expression of the CDK1-cyclin Clb2
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
reduced kinase activity of polo kinase Cdc5 affects chromosome stability and DNA damage response. Cdc5-T238A mutant cells have increased rate of chromosome loss and gross chromosomal rearrangements, indicating altered genome stability. The T238A mutation affects timely localization of Cdc5 to the spindle pole bodies and blocks cell cycle restart after one irreparable double-strand break. In cells responding to alkylating agent metylmethane sulfonate (MMS), the cdc5-T238A mutation reduces the phosphorylation of Mus81-Mms4 resolvase and exacerbates the MMS sensitivity of sgs1D cells that accumulate Holliday junctions. Rad53 dephosphorylation is severely impaired in cdc5-T238A cells till almost 20-22 hours, but the defect is less severe than in cdc5-ad mutant cells. Cdc5-T238A and Cdc5-ad mutant protein variants show altered localization to spindle pole bodies after one irreparable double strand break. Mutant phenotypes, overview
metabolism
the enzyme affects the Mus81-Mms4 mediated resolution pathway
physiological function
physiological function
physiological function
Cdc5 contributes to the timely release of Cdc14 in mitosis. Cdc5 acts in parallel with MEN during anaphase. The MEN-independent Cdc5 function requires active separase and activation by Cdk1-dependent phosphorylation. The Cdc5 function is regulated by sequential Cdk1 phosphorylation. Initial phosphorylation at T242 activates Cdc5, which, in turn, promotes Cdc14 release in the metaphase-to-anaphase transition. Cdc14 release on Cdc5 induction does require active Cdc5 kinase activity, and Cdc5-induced Cdc14 release requires Cdc28-Clb2 activity. Phosphorylation at T70 contributes to Cdc5-MEN function in late anaphase. Cdc5 requires separase to induce Cdc14 release from the nucleolus
physiological function
polo-like kinases control several aspects of eukaryotic cell division and DNA damage response. Cdc5 is the only PLK in Saccharomyces cerevisiae, it has minor effect on cell growth in unperturbed conditions. It is important of regulate Cdc5 activity through T-loop phosphorylation to preserve genome integrity and respond to DNA damage. Cdc5 may phosphorylate and regulate several factors that can suppress gross chromosomal rearrangements
physiological function
-
Cdc5 plays multiple roles during the cell cycle, component of the fourteen early anaphase release, FEAR, pathway, degradation of the protein Swe1 is Cdc5 dependent
physiological function
-
Plks are potent regulators of M phase, their roles in mitotic entry, spindle pole functions and cytokinesis are broadly conserved
physiological function
-
promotes adaptation to the DNA damage checkpoint, in addition to its numerous roles in mitotic progression
physiological function
-
enzyme Cdc5 is required for spindle integrity during checkpoint bypass, it is not required for meiosis checkpoint activation
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
Cdc5 function is regulated by sequential Cdk1 phosphorylation initially mostly at T242 and T238. Initial phosphorylation at T242 activates Cdc5 promotes Cdc14 release , and phosphorylation at T70 contributes to Cdc5-MEN function
phosphoprotein
phosphorylation of threonine residues in the T-loop of the kinase domain is pivotal for PLKs activation. Phosphorylation of T238 site of Cdc5 is dispensable for cell viability
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
L251W
generation of mutant cdc5-ad that has a checkpoint adaptation defective allele, i.e. it blocks DNA damage checkpoint adaptation, cdc5-ad does not show reduced kinase activity, defective Mms4 phosphorylation and genetic interaction with sgs1DELTA
T238A
the substitution in the T-loop reduces the kinase activity of Cdc5. Mutant cdc5-T238A cells do not adapt to one irreparable double strand break and uncapped telomere, cdc5-T238A affects Mms4 phosphorylation and viability of sgs1D cells with alkylating agent metylmethane sulfonate
W565R
single point mutation within the PB1 motif of the highly conserved polo box domain, mutant exhibits a temperature-sensitive growth defect
additional information
additional information
-
in mutant cells in which the Cdc5 promoter is exchanged for the Clb2 promoter, the enzyme is degradated during G1 phase and is absent in meiosis, Cdc5-depleted cells progress through premeiotic S phase and enter metaphase I but arrest in metaphase I, mechanism
additional information
-
overexpression of Cdc5 leads to Cdc14 release from the nucleolus in S-phase-arrested cells
additional information
-
overexpression of mutant or wild-type Cdc5 results in multinucleated cells, Cdc5 overexpression overrides checkpoint-induced cell cycle arrest, Cdc5-defective mutant protein suppresses a Rad53 checkpoint defect
additional information
-
mutants lacking Cdc5, contractile actin ring assembly is impaired
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant expression of GFP-tagged wild-type enzyme and mutants in Saccharomyces cerevisiae strain with JKM139 background. Mutants Cdc5-T238A and Cdc5-ad variants, as well as the wild-type protein, were detectable in late S and G2/M phases, but not in late G1 and early S, mirroring the expression of the CDK1-cyclin Clb2
EGFP-tagged Cdc5 protein is expressed by high copy plasmid pRS424, 425 or 426 under control of authentic promoter
-
expression of CDC5 fused to the Met3 promoter intergrated in the LEU2 locus of a yeast strain carrying a null allele of CDC5
-
GAL-HA3-cdc5, GAL-HA3-cdc5-K110A, and GAL-HA3-cdc5-ad are integrated into the plasmids pDM164, pDM173, and pDM191, respectively
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
polo-like kinases are overexpressed in several types of cancer and are a marker of bad prognosis
additional information
additional information
-
Cdc5 is required to establish contractile actin ring assembly and to maintain it. Cdc5 controls the targeting and activation of Rho1 at the division site via Rho1 guanine nucleotide exchange factors Tus1 and Rom2
additional information
-
Cdc5p is required for the production of key mitotic regulators
additional information
-
only one polo kinase found, is a master mitotic regulator, involved in the regulation of mitotic entry, the metaphase to anaphase transition, mitotic exit and cytokinesis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kitada, K.; Johnson, A.L.; Johnston, L.H.; Sugino, A.
A multicopy suppressor gene of the Saccharomyces cerevisiae G1 cell cycle mutant gene dbf4 encodes a protein kinase and is identified as CDC5
Mol. Cell. Biol.
13
4445-4457
1993
Saccharomyces cerevisiae (P32562)
Rancati, G.; Crispo, V.; Lucchini, G.; Piatti, S.
Mad3/BubR1 phosphorylation during spindle checkpoint activation depends on both Polo and Aurora kinases in budding yeast
Cell Cycle
4
972-980
2005
Saccharomyces cerevisiae
Visintin, R.; Stegmeier, F.; Amon, A.
The role of the polo kinase Cdc5 in controlling Cdc14 localization
Mol. Biol. Cell
14
4486-4498
2003
Saccharomyces cerevisiae
Xie, S.; Xie, B.; Lee, M.Y.; Dai, W.
Regulation of cell cycle checkpoints by polo-like kinases
Oncogene
24
277-286
2005
Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Schizosaccharomyces pombe, Xenopus laevis
Lee, B.H.; Amon, A.
Role of polo-like kinase CDC5 in programming meiosis I chromosome segregation
Science
300
482-486
2003
Saccharomyces cerevisiae
Zimmerman, W.C.; Erikson, R.L.
Finding Plk3
Cell Cycle
6
1314-1318
2007
Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens (P53350), Homo sapiens (Q9H4B4), Homo sapiens (Q9NYY3)
Darieva, Z.; Bulmer, R.; Pic-Taylor, A.; Doris, K.S.; Geymonat, M.; Sedgwick, S.G.; Morgan, B.A.; Sharrocks, A.D.
Polo kinase controls cell-cycle-dependent transcription by targeting a coactivator protein
Nature
444
494-498
2006
Saccharomyces cerevisiae
Yoshida, S.; Kono, K.; Lowery, D.M.; Bartolini, S.; Yaffe, M.B.; Ohya, Y.; Pellman, D.
Polo-like kinase Cdc5 controls the local activation of Rho1 to promote cytokinesis
Science
313
108-111
2006
Saccharomyces cerevisiae
Park, C.J.; Park, J.E.; Karpova, T.S.; Soung, N.K.; Yu, L.R.; Song, S.; Lee, K.H.; Xia, X.; Kang, E.; Dabanoglu, I.; Oh, D.Y.; Zhang, J.Y.; Kang, Y.H.; Wincovitch, S.; Huffaker, T.C.; Veenstra, T.D.; McNally, J.G.; Lee, K.S.
Requirement for the budding yeast polo kinase Cdc5 in proper microtubule growth and dynamics
Eukaryot. Cell
7
444-453
2008
Saccharomyces cerevisiae (P32562), Saccharomyces cerevisiae
Crasta, K.; Lim, H.H.; Giddings, T.H.; Winey, M.; Surana, U.
Inactivation of Cdh1 by synergistic action of Cdk1 and polo kinase is necessary for proper assembly of the mitotic spindle
Nat. Cell Biol.
10
665-675
2008
Saccharomyces cerevisiae
Nakashima, A.; Maruki, Y.; Imamura, Y.; Kondo, C.; Kawamata, T.; Kawanishi, I.; Takata, H.; Matsuura, A.; Lee, K.S.; Kikkawa, U.; Ohsumi, Y.; Yonezawa, K.; Kamada, Y.
The yeast Tor signaling pathway is involved in G2/M transition via polo-kinase
PLoS ONE
3
e2223
2008
Saccharomyces cerevisiae
Liang, F.; Jin, F.; Liu, H.; Wang, Y.
The molecular function of the yeast polo-like kinase Cdc5 in Cdc14 release during early anaphase
Mol. Biol. Cell
20
3671-3679
2009
Saccharomyces cerevisiae
Archambault, V.; Glover, D.
Polo-like kinases: Conservation and divergence in their functions and regulation
Nat. Rev. Mol. Cell Biol.
10
265-275
2009
Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Saccharomyces pombe, Xenopus laevis
Vidanes, G.M.; Sweeney, F.D.; Galicia, S.; Cheung, S.; Doyle, J.P.; Durocher, D.; Toczyski, D.P.
CDC5 inhibits the hyperphosphorylation of the checkpoint kinase Rad53, leading to checkpoint adaptation
PLoS Biol.
8
e1000286
2010
Saccharomyces cerevisiae
Iacovella, M.G.; Daly, C.N.; Kelly, J.S.; Michielsen, A.J.; Clyne, R.K.
Analysis of Polo-like kinase Cdc5 in the meiosis recombination checkpoint
Cell Cycle
9
1182-1193
2010
Saccharomyces cerevisiae
Rawal, C.C.; Riccardo, S.; Pesenti, C.; Ferrari, M.; Marini, F.; Pellicioli, A.
Reduced kinase activity of polo kinase Cdc5 affects chromosome stability and DNA damage response in S. cerevisiae
Cell Cycle
15
2906-2919
2016
Saccharomyces cerevisiae (P32562), Saccharomyces cerevisiae
Rodriguez-Rodriguez, J.A.; Moyano, Y.; Jativa, S.; Queralt, E.
Mitotic exit function of polo-like kinase Cdc5 is dependent on sequential activation by Cdk1
Cell Rep.
15
2050-2062
2016
Saccharomyces cerevisiae (P32562), Saccharomyces cerevisiae
Chauhan, S.; Samanta, S.; Sharma, N.; Thakur, J.K.; Dev, K.; Sourirajan, A.
Saccharomyces cerevisiae polo-like kinase, Cdc5 exhibits ATP-dependent Mg2+-enhanced kinase activity in vitro
Heliyon
5
e03050
2019
Saccharomyces cerevisiae
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