Names & Taxonomy

Uniprot ID:
P53350
Entry Name:
PLK1_HUMAN
Status:
reviewed
Protein Names:
Serine/threonine-protein kinase PLK1 (EC 2.7.11.21) (Polo-like kinase 1) (PLK-1) (Serine/threonine-protein kinase 13) (STPK13)
Gene Names:
PLK1 PLK
Gene Names Primary:
PLK1
Organism:
Homo sapiens (Human)

Structure

Length:
603
Sequence:
MSAAVTAGKLARAPADPGKAGVPGVAAPGAPAAAPPAKEIPEVLVDPRSRRRYVRGRFLGKGGFAKCFEISDADTKEVFAGKIVPKSLLLKPHQREKMSMEISIHRSLAHQHVVGFHGFFEDNDFVFVVLELCRRRSLLELHKRRKALTEPEARYYLRQIVLGCQYLHRNRVIHRDLKLGNLFLNEDLEVKIGDFGLATKVEYDGERKKTLCGTPNYIAPEVLSKKGHSFEVDVWSIGCIMYTLLVGKPPFETSCLKETYLRIKKNEYSIPKHINPVAASLIQKMLQTDPTARPTINELLNDEFFTSGYIPARLPITCLTIPPRFSIAPSSLDPSNRKPLTVLNKGLENPLPERPREKEEPVVRETGEVVDCHLSDMLQQLHSVNASKPSERGLVRQEEAEDPACIPIFWVSKWVDYSDKYGLGYQLCDNSVGVLFNDSTRLILYNDGDSLQYIERDGTESYLTVSSHPNSLMKKITLLKYFRNYMSEHLLKAGANITPREGDELARLPYLRTWFRTRSAIILHLSNGSVQINFFQDHTKLILCPLMAAVTYIDEKRDFRTYRLSLLEEYGCCKELASRLRYARTMVDKLLSSRSASNRLKAS
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Nucleus. Chromosome, centromere, kinetochore. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle. Midbody. Note=During early stages of mitosis, the phosphorylated form is detected on centrosomes and kinetochores. Localizes to the outer kinetochore. Presence of SGOL1 and interaction with the phosphorylated form of BUB1 is required for the kinetochore localization. Localizes onto the central spindle by phosphorylating and docking at midzone proteins KIF20A/MKLP2 and PRC1. Colocalizes with FRY to separating centrosomes and spindle poles from prophase to metaphase in mitosis, but not in other stages of the cell cycle.

Function

Function:
Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis. Polo-like kinase proteins acts by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, PPP1R12A/MYPT1, PRC1, RACGAP1/CYK4, SGOL1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1 and WEE1. Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating KIZ, NEDD1 and NINL. NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins. Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1. Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains. Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation. Promotes the central spindle recruitment of ECT2. Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1. Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1. Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase. Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity. Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2. PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation. Required for kinetochore localization of BUB1B. Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2. Phosphorylates SGOL1: required for spindle pole localization of isoform 3 of SGOL1 and plays a role in regulating its centriole cohesion function. Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome. Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53. Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA. Contributes to the regulation of AURKA function. Also required for recovery after DNA damage checkpoint and entry into mitosis. Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning (PubMed:8991084, PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069). Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage (By similarity). Phosphorylates CEP68 and is required for its degradation (PubMed:25503564).
Catalytic Activity:
ATP + a protein = ADP + a phosphoprotein.
Enzyme Regulation:
ENZYME REGULATION: Activated by phosphorylation of Thr-210 by AURKA; phosphorylation by AURKA is enhanced by BORA. Once activated, activity is stimulated by binding target proteins. Binding of target proteins has no effect on the non-activated kinase. Several inhibitors targeting PLKs are currently in development and are under investigation in a growing number of clinical trials, such as BI 2536, an ATP-competitive PLK1 inhibitor or BI 6727, a dihydropteridinone that specifically inhibits the catalytic activity of PLK1.
Active Site:
ACT_SITE 176 176 Proton acceptor.
Gene Ontology Go:
centrosome
chromatin
condensed nuclear chromosome outer kinetochore
cytoplasm
cytosol
kinetochore
microtubule cytoskeleton
midbody
nucleolus
nucleoplasm
nucleus
spindle
spindle midzone
spindle pole
synaptonemal complex
anaphase-promoting complex binding
ATP binding
kinase activity
microtubule binding
protein kinase activity
protein kinase binding
protein serine/threonine kinase activity
activation of APC-Cdc20 complex activity
anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
cell proliferation
centrosome organization
cytokinesis
establishment of protein localization
female meiosis chromosome segregation
G2 DNA damage checkpoint
G2/M transition of mitotic cell cycle
homologous chromosome segregation
metaphase/anaphase transition of mitotic cell cycle
microtubule bundle formation
mitotic cell cycle
mitotic cytokinesis
mitotic nuclear division
mitotic nuclear envelope disassembly
mitotic sister chromatid segregation
mitotic spindle assembly checkpoint
negative regulation of apoptotic process
negative regulation of cyclin-dependent protein serine/threonine kinase activity
negative regulation of transcription from RNA polymerase II promoter
organelle organization
peptidyl-serine phosphorylation
positive regulation of peptidyl-threonine phosphorylation
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
positive regulation of proteolysis
positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition
positive regulation of ubiquitin-protein transferase activity
protein destabilization
protein localization to chromatin
protein phosphorylation
protein ubiquitination
regulation of cell cycle
regulation of mitotic cell cycle
regulation of mitotic metaphase/anaphase transition
regulation of mitotic spindle assembly
regulation of protein binding
regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
small GTPase mediated signal transduction
synaptonemal complex disassembly
Gene Ontology Biological Process:
activation of APC-Cdc20 complex activity
anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
cell proliferation
centrosome organization
cytokinesis
establishment of protein localization
female meiosis chromosome segregation
G2/M transition of mitotic cell cycle
G2 DNA damage checkpoint
homologous chromosome segregation
metaphase/anaphase transition of mitotic cell cycle
microtubule bundle formation
mitotic cell cycle
mitotic cytokinesis
mitotic nuclear division
mitotic nuclear envelope disassembly
mitotic sister chromatid segregation
mitotic spindle assembly checkpoint
negative regulation of apoptotic process
negative regulation of cyclin-dependent protein serine/threonine kinase activity
negative regulation of transcription from RNA polymerase II promoter
organelle organization
peptidyl-serine phosphorylation
positive regulation of peptidyl-threonine phosphorylation
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
positive regulation of proteolysis
positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition
positive regulation of ubiquitin-protein transferase activity
protein destabilization
protein localization to chromatin
protein phosphorylation
protein ubiquitination
regulation of cell cycle
regulation of mitotic cell cycle
regulation of mitotic metaphase/anaphase transition
regulation of mitotic spindle assembly
regulation of protein binding
regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
small GTPase mediated signal transduction
synaptonemal complex disassembly
Gene Ontology Molecular Function:
anaphase-promoting complex binding
ATP binding
kinase activity
microtubule binding
protein kinase activity
protein kinase binding
protein serine/threonine kinase activity
Gene Ontology Cellular Component:
centrosome
chromatin
condensed nuclear chromosome outer kinetochore
cytoplasm
cytosol
kinetochore
microtubule cytoskeleton
midbody
nucleolus
nucleoplasm
nucleus
spindle
spindle midzone
spindle pole
synaptonemal complex
Keywords:
3D-structure
ATP-binding
Acetylation
Cell cycle
Cell division
Centromere
Chromosome
Complete proteome
Cytoplasm
Cytoskeleton
Isopeptide bond
Kinase
Kinetochore
Mitosis
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Serine/threonine-protein kinase
Transferase
Ubl conjugation
Interacts With:
Q99IB8; Q9NR09; O96017; Q60838; P23588; Q2NKX8; O60447; Q13158; Q9NYZ3; P08107; P33993; Q00987; P23804; Q8TD19; O75665; Q8IXK0; Q8IY92; Q92844; P04637

Publication

PubMed ID:
8018557 7902533 7962193 8127874 15489334 7478607 9083047 8991084 11202906 12207013 12447691 12442251 12852856 12639966 12738781 12939256 12524548 14734534 15469984 15070733 15148369 16198290 15616186 16439210 16760428 16980960 16247472 17081991 16645325 17981789 17218258 17617734 17310276 17376779 17943598 17351640 17495026 18662541 18329369 18418051 18521620 18331714 18477460 18174154 19029337 18691976 19160488 18615013 18669648 19596235 19473992 19509060 19351716 19369195 19468300 19468302 20671765 20068231 21269460 21402792 22753416 22814378 23455152 23509069 23455478 25503564 14532005 14592974 17461553 18005335 17307877 18391401 19597481 17344846