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Information on EC 2.7.11.21 - polo kinase and Organism(s) Drosophila melanogaster and UniProt Accession O97143
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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
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pericentriolar
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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: Drosophila melanogaster
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
FGF-inducible kinase
-
-
-
-
Polo kinase
Proliferation-related kinase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
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 + Asterless protein
ADP + phosphorylated Asterless protein
isoform Plk4 phosphorylates the N-terminal domain of Asterless protein
-
-
?
ATP + 85kDa microtubule-associated protein
ADP + phosphorylated 85kDa microtubule-associated protein
ATP + 85kDa microtubule-associated protein
ADP + phosphorylated 85kDa microtubule-associated protein
-
-
-
-
?
ATP + 85kDa microtubule-associated protein
ADP + phosphorylated 85kDa microtubule-associated protein
-
protein is released from microtubules after phosphorylation
-
-
?
ATP + abnormal spindle pole protein
ADP + phosphorylated abnormal spindle pole protein
-
-
-
-
?
ATP + abnormal spindle pole protein
ADP + phosphorylated abnormal spindle pole protein
-
i.e. abnormal spindle pole protein, activation of abnormal spindle pole protein by phosphorylation
-
-
?
ATP + dephospho-beta-tubulin
ADP + phosphorylated beta-tubulin
-
-
-
-
?
ATP + dephospho-beta-tubulin
ADP + phosphorylated beta-tubulin
-
the enzyme is required for beta-tubulin recruitment to the centrosome
-
-
?
ATP + MEI-S332 protein
ADP + phosphorylated MEI-S332 protein
-
substrate is a protein essential in meiosis for maintaining cohesion at centromers until sister chromatids separate at the metaphase II/anaphase II transition, phosphorylation by polo kinase removes the protein from centromeres and antagonizes the MEI-S332 function, MEI-S332 phosphorylation by polo kinase is essential for viability of the cells
-
-
?
ATP + MEI-S332 protein
ADP + phosphorylated MEI-S332 protein
-
enzyme requires residues T331 and possibly in combination with S234 for activity, no activity with MEI-S332 protein mutants T331A and S234A/T331A in S2 cells
-
-
?
additional information
?
-
autophosphorylation of wild-type full-length enzyme and isolated kinase domain
-
-
?
additional information
?
-
normal bipolar spindles with polyploid complements of chromosomes, bipolar spindles in which one pole can be unusually broad, and monopolar spindles
-
-
?
additional information
?
-
mutation in polo leads to a variety of abnormal mitoses in Drosophila larval neuroblasts. These include otherwise normal looking mitotic spindles upon which chromosomes appear overcondensed
-
-
?
additional information
?
-
-
the enzyme is a mitotic kinase and is required for centrosome maturation at mitotic M-phase entry in order to recruit the gamma-tubulin ring complex and activate abnormal spindle pole protein, Asp, the enzyme is involved in mitotic networks and cytokinesis, e.g. in spermatogenesis, overview, functional modeling of polo kinase in mitotic phases
-
-
?
additional information
?
-
-
the enzyme is pivotal in cell division as a regulator of cell cycle checkpoints in mitotic progression, regulation of cytokinesis, 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 + 85kDa microtubule-associated protein
ADP + phosphorylated 85kDa microtubule-associated protein
-
protein is released from microtubules after phosphorylation
-
-
?
ATP + abnormal spindle pole protein
ADP + phosphorylated abnormal spindle pole protein
-
i.e. abnormal spindle pole protein, activation of abnormal spindle pole protein by phosphorylation
-
-
?
ATP + dephospho-beta-tubulin
ADP + phosphorylated beta-tubulin
-
the enzyme is required for beta-tubulin recruitment to the centrosome
-
-
?
ATP + MEI-S332 protein
ADP + phosphorylated MEI-S332 protein
-
substrate is a protein essential in meiosis for maintaining cohesion at centromers until sister chromatids separate at the metaphase II/anaphase II transition, phosphorylation by polo kinase removes the protein from centromeres and antagonizes the MEI-S332 function, MEI-S332 phosphorylation by polo kinase is essential for viability of the cells
-
-
?
additional information
?
-
normal bipolar spindles with polyploid complements of chromosomes, bipolar spindles in which one pole can be unusually broad, and monopolar spindles
-
-
?
additional information
?
-
mutation in polo leads to a variety of abnormal mitoses in Drosophila larval neuroblasts. These include otherwise normal looking mitotic spindles upon which chromosomes appear overcondensed
-
-
?
additional information
?
-
-
the enzyme is a mitotic kinase and is required for centrosome maturation at mitotic M-phase entry in order to recruit the gamma-tubulin ring complex and activate abnormal spindle pole protein, Asp, the enzyme is involved in mitotic networks and cytokinesis, e.g. in spermatogenesis, overview, functional modeling of polo kinase in mitotic phases
-
-
?
additional information
?
-
-
the enzyme is pivotal in cell division as a regulator of cell cycle checkpoints in mitotic progression, regulation of cytokinesis, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Asterless-A-13PM
phosphomimetic Asterless-A (13PM) inhibits isoform Plk4 activity by autophosphorylation of isoform Plk4 s kinase domain
-
Map205
-
Map205 can stabilize Polo and inhibit its cellular activity in vivo
-
matrimony
the matrimony protein acts as a negative regulator of polo during the later stages of G2 arrest during meiosis
-
additional information
Plk4 possesses an autoinhibitory mechanism mediated by a linker (L1) near the kinase domain, newly synthesized Plk4 is autoinhibited by L1. Autoinhibition is a conserved feature of Plks. In the case of Plk4, autoinhibition is relieved after homodimerization and is accomplished by PB3 and by autophosphorylation of L1. In contrast, autophosphorylation of the second linker promotes separation of the Plk4 homodimer. Mechanism for Plk4 autoinhibition, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Asterless-A-13A
phospho-null Asterless-A (13A) stimulates kinase activity by relieving L1-mediated isoform Plk4 autoinhibition
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
polo kinase undergoes cell cycle-dependent changes in its distribution. It is predominantly cytoplasmic during interphase, it becomes associated with condensed chromosomes toward the end of prophase, and it remains associated with chromosomes until telophase, whereupon it becomes cytoplasmic
polo kinase undergoes cell cycle-dependent changes in its distribution. It is predominantly cytoplasmic during interphase, it becomes associated with condensed chromosomes toward the end of prophase, and it remains associated with chromosomes until telophase, whereupon it becomes cytoplasmic
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
kinase activity is impaired in Plk4-DELTAPB3, polo box 3-mutated enzyme, reducing its ability to transautophosphorylate and recruit Slimb and thereby increasing its stability
physiological function
polo-like kinase 4 is a master regulator of centriole duplication, and its hyperactivity induces centriole amplification. Homodimeric Plk4 is ubiquitinated as a result of autophosphorylation, promoting its own degradation and preventing centriole amplification. Speculative multistep model for Plk4 activation and regulation, overview
malfunction
phenotype of different polo allele combinations compared to the effect of chemical inhibition. The chromosomal passenger complex is mislocalized in polo mutant meiosis. This defective CPC localization is independent of the degree of disruption of the spindle midzone, as visualized by staining for microtubules
physiological function
additional information
the three polo boxes of Plk4 not only are crucial for Plk4 homodimerization and ubiquitination but also relieve autoinhibition caused by linker 1. Polo box 3 is required for kinase activity
physiological function
-
Plks are potent regulators of M phase, their roles in mitotic entry, spindle pole functions and cytokinesis are broadly conserved
physiological function
polo kinase regulates the localization and activity of the chromosomal passenger complex in meiosis and mitosis, e.g. in larval neuroblast mitoses, significant differences in the localization and activity of the chromosomal passenger complex in diploid tissues. Polo kinase is required for the correct localization and activity of the CPC at all stages of male meiosis as well as in larval neuroblast mitoses
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PLK4_DROME
769
0
85887
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
the three polo boxes of Plk4 are crucial for Plk4 homodimerization
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
the enzyme performs autophosphorylation. Plk4 phosphorylation pattern, overview
ubiquitination
polo box 1, PB1, of Plk4 contains multiple ubiquitination sites. At least some of the Lys in PB1 are physiologically important targets of Plk4 ubiquitination, overview
phosphoprotein
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S374A/S378A
site-directed mutagenesis within L1 (GST-L1-Ala-602), the double mutant shows reduced enzyme activity compared to the wild-type enzyme
additional information
additional information
complete inactivation of a kinase domain mutant. Expression of Plk4 phospho-mutants influences centriole numbers
additional information
-
male homozygous polo mutant flies die in the third instar larval stage, heterozygous mutants show affected centromer dissociation of MEI-S332, but not association resulting in chromosome segragation defects
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant C-terminally FLAG-His6-tagged polo kinase domain of Plk4 fromherichia coli strain BL21(DE3) by nickel affinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant expression of full-length Plk4, subcloned into a pMT vector containing an in-frame coding sequence for EGFP or myc and the inducible metallothionein promoter, in Drosophila S2 cells, recombinant expression of the C-terminally FLAG-His6-tagged polo kinase domain of Plk4 in Escherichia coli strain BL21(DE3)
expression of GST-tagged Plx1 in S2 cells, co-expression with GFP-tagged MEI-S332
-
into the pDONR221lambda entry vector, the gene is recombined in different destination vectors for expression in fusion with GFP or protein A
-
the polo fragment is cloned into pBluescript and subcloned into the pUASP vector to generate transgenic flies
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
Adams, M.D.; Celniker, S.E.; Holt, R.A.; Evans, C.A.; Gocayne, J.D.; et al.
The genome sequence of Drosophila melanogaster
Science
287
2185-2195
2000
Drosophila melanogaster (P52304)
Llamazares, S.; Moreira, A.; Tavares, A.; et al.
Polo encodes a protein kinase homolog required for mitosis in Drosophila
Genes Dev.
5
2153-2165
1991
Drosophila melanogaster (P52304)
Clarke, A.S.; Tang, T.T.; Ooi, D.L.; Orr-Weaver, T.L.
POLO kinase regulates the Drosophila centromere cohesion protein MEI-S332
Dev. Cell
8
53-64
2005
Drosophila melanogaster, Xenopus laevis
Glover, D.M.
Polo kinase and progression through M phase in Drosophila: a perspective from the spindle poles
Oncogene
24
230-237
2005
Drosophila melanogaster
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
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)
Archambault, V.; Davino, P.P.; Deery, M.J.; Lilley, K.S.; Glover, D.M.
Sequestration of Polo kinase to microtubules by phosphopriming-independent binding to Map205 is relieved by phosphorylation at a CDK site in mitosis
Genes Dev.
22
2707-2720
2008
Drosophila melanogaster
Xiang, Y.; Takeo, S.; Florens, L.; Hughes, S.E.; Huo, L.J.; Gilliland, W.D.; Swanson, S.K.; Teeter, K.; Schwartz, J.W.; Washburn, M.P.; Jaspersen, S.L.; Hawley, R.S.
The inhibition of polo kinase by matrimony maintains G2 arrest in the meiotic cell cycle
PLoS Biol.
5
e323
2007
Drosophila melanogaster (P52304)
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
Carmena, M.; Lombardia, M.O.; Ogawa, H.; Earnshaw, W.C.
Polo kinase regulates the localization and activity of the chromosomal passenger complex in meiosis and mitosis in Drosophila melanogaster
Open Biology
4
140162
2014
Drosophila melanogaster (P52304), Drosophila melanogaster
Klebba, J.E.; Buster, D.W.; McLamarrah, T.A.; Rusan, N.M.; Rogers, G.C.
Autoinhibition and relief mechanism for polo-like kinase 4
Proc. Natl. Acad. Sci. USA
112
E657-E666
2015
Drosophila melanogaster (O97143)
Boese, C.J.; Nye, J.; Buster, D.W.; McLamarrah, T.A.; Byrnes, A.E.; Slep, K.C.; Rusan, N.M.; Rogers, G.C.
Asterless is a polo-like kinase 4 substrate that both activates and inhibits kinase activity depending on its phosphorylation state
Mol. Biol. Cell
29
2874-2886
2018
Drosophila melanogaster (O97143)
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