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serine/threonine protein kinase PLK1; polo-like kinase 1; PLK-1; serine/threonine protein kinase 13; STPK13 (PLK1 PLK)

Function: - serine/threonine protein kinase - performs several functions throughout M phase of the cell cycle, including a) regulation of centrosome maturation & spindle assembly b) removal of cohesins from chromosome arms c) inactivation of APC/C inhibitors & activation of anaphase-promoting complex/cyclosome d) regulation of mitotic exit & cytokinesis - required for recovery after DNA damage checkpoint & entry into mitosis - required for kinetochore localization of BUB1B - phosphorylates SGOL1 - required for spindle pole localization of isoform 3 of SGOL1 & plays a role in regulating its centriole cohesion function - phosphorylates BORA, thus promotes the degradation of BORA - contributes to the regulation of AURKA - regulates TP53 stability through phosphorylation of TOPORS - phosphorylates NEDD1 - NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, a step in spindle formation - activated by serine & threonine phosphorylation - once activated, activity is stimulated by binding target proteins - binding of target proteins has no effect on the non-activated kinase - catalytic activity is enhanced by phosphorylation of Thr-210 - phosphorylation at Thr-210 is first detected on centrosomes in the G2 phase of the cell cycle, peaks in prometaphase & gradually disappears from centrosomes during anaphase - autophosphorylation & phosphorylation of Ser-137 may not be significant for the activation of PLK1 during mitosis, but may enhance catalytic activity during recovery after DNA damage checkpoint - ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) in anaphase & following DNA damage, leading to its degradation by the proteasome - ubiquitination is mediated via its interaction with FZR1/CDH1 - ubiquitination & subsequent degradation prevents entry into mitosis & is essential to maintain an efficient G2 DNA damage checkpoint - interacts with CEP170 & EVI5 - interacts & phosphorylates ERCC6L - interacts with FAM29A - interacts with SLX4/BTBD12 & TTDN1 - interacts with BUB1B - interacts (via POLO-box domain) with the phosphorylated form of BUB1, MLF1IP & CDC25C - interacts with isoform 3 of SGOL1 - interacts with BORA, KIF2A & AURKA - interacts with TOPORS & CYLD Structure: - belongs to the protein kinase superfamily, Ser/Thr protein kinase family, CDC5/polo subfamily - contains 2 POLO box domains - contains 1 protein kinase domain Compartment: - nucleus, chromosome, centromere, kinetochore - cytoplasm, cytoskeleton, centrosome - during early stages of mitosis, the phosphorylated form is detected on centrosomes & kinetochores - localizes to the outer kinetochore - SGOL1 interaction with the phosphorylated form of BUB1 is required for the kinetochore localization Expression: - placenta & colon - accumulates to a maximum during the G2 & M phases - declines to a nearly undetectable level following mitosis & throughout G1 phase - begins to accumulate again during S phase - induced by growth-stimulating agents

General

nuclear protein serine/threonine kinase

Properties

SIZE: entity length = 603 aa MW = 68 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Thr phosphorylation site {T6} kinase domain SITE: 53-305 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 59-67 ATP-binding site NAME: ATP-binding site SITE: 82-82 Ser phosphorylation site {S103} ATP-binding site NAME: ATP-binding site SITE: 131-131 Ser phosphorylation site {S137} aspartate residue {D176} ATP-binding site NAME: ATP-binding site SITE: 178-181 Activation loop {194-221} ATP-binding site NAME: ATP-binding site SITE: 194-194 Thr phosphorylation site {T210} Thr phosphorylation site {T214} Ser phosphorylation site {S269} Ser phosphorylation site {S335} ubiquitination site (destruction box, D-box) SITE: 337-340 FOR-BINDING-OF: ubiquitin Ser phosphorylation site {S375} POLO box domain {417-480} MOTIF: Ser phosphorylation site {S450} Ser phosphorylation site {S461} Thr phosphorylation site {T464} Linker {493-507} MOTIF: Thr phosphorylation site {T498} POLO box domain {515-584} MOTIF: domain {538-540} STATE: active state

Database Correlations

OMIM 602098 UniProt P53350 PFAM correlations Entrez Gene 5347 Kegg hsa:5347 ENZYME 2.7.11.21

References

  1. UniProt :accession P53350
  2. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/PLK1ID41747ch16p12.html
  3. Jallepalli & Lengauer. Chromsosome segregation and cancer: cutting through the mystery Nature Reviews Cancer 1:109-117, 2001 PMID: 11905802

Component-of

SKAP complex; astrin-kinastrin complex; SPAG5-kinastrin complex