InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PLK1

Summary

InnateDB Protein

IDBP-20744.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PLK1

Protein Name

polo-like kinase 1

Synonyms

PLK; STPK13;

Species

Homo sapiens

Ensembl Protein

ENSP00000300093

InnateDB Gene

IDBG-20740 (PLK1)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:11202906, ECO:0000269PubMed:12207013, ECO:0000269PubMed:12447691, ECO:0000269PubMed:12524548, ECO:0000269PubMed:12738781, ECO:0000269PubMed:12852856, ECO:0000269PubMed:12939256, ECO:0000269PubMed:14532005, ECO:0000269PubMed:14734534, ECO:0000269PubMed:15070733, ECO:0000269PubMed:15148369, ECO:0000269PubMed:15469984, ECO:0000269PubMed:16198290, ECO:0000269PubMed:16247472, ECO:0000269PubMed:16980960, ECO:0000269PubMed:17081991, ECO:0000269PubMed:17351640, ECO:0000269PubMed:17376779, ECO:0000269PubMed:17617734, ECO:0000269PubMed:18174154, ECO:0000269PubMed:18331714, ECO:0000269PubMed:18418051, ECO:0000269PubMed:18477460, ECO:0000269PubMed:18521620, ECO:0000269PubMed:18615013, ECO:0000269PubMed:19160488, ECO:0000269PubMed:19351716, ECO:0000269PubMed:19468300, ECO:0000269PubMed:19468302, ECO:0000269PubMed:19473992, ECO:0000269PubMed:19509060, ECO:0000269PubMed:19597481, ECO:0000269PubMed:23455478, ECO:0000269PubMed:23509069, ECO:0000269PubMed:8991084}.

Subcellular Localization

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.

Disease Associations

Note=Defects in PLK1 are associated with some cancers, such as gastric, thyroid or B-cell lymphomas. Expression is cancer increased in tumor tissues with a poor prognosis, suggesting a role in malignant transformations and carcinogenesis.

Tissue Specificity

Placenta and colon.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 261 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.

Experimentally validated
Total	261 [view]
Protein-Protein	251 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	8 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	6 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008017	microtubule binding
GO:0010997	anaphase-promoting complex binding
GO:0016301	kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019901	protein kinase binding

Biological Process

GO:0000070	mitotic sister chromatid segregation
GO:0000086	G2/M transition of mitotic cell cycle
GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0000278	mitotic cell cycle
GO:0000281	mitotic cytokinesis
GO:0000910	cytokinesis
GO:0001578	microtubule bundle formation
GO:0006468	protein phosphorylation
GO:0007067	mitotic nuclear division
GO:0007077	mitotic nuclear envelope disassembly
GO:0007091	metaphase/anaphase transition of mitotic cell cycle
GO:0007092	activation of mitotic anaphase-promoting complex activity
GO:0007094	mitotic spindle assembly checkpoint
GO:0007346	regulation of mitotic cell cycle
GO:0008283	cell proliferation
GO:0010800	positive regulation of peptidyl-threonine phosphorylation
GO:0016567	protein ubiquitination
GO:0018105	peptidyl-serine phosphorylation
GO:0030071	regulation of mitotic metaphase/anaphase transition
GO:0031145	anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
GO:0031572	G2 DNA damage checkpoint
GO:0031648	protein destabilization
GO:0032436	positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0040038	polar body extrusion after meiotic divisions
GO:0043066	negative regulation of apoptotic process
GO:0043393	regulation of protein binding
GO:0045087	innate immune response (InnateDB)
GO:0045184	establishment of protein localization
GO:0045736	negative regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0045862	positive regulation of proteolysis
GO:0046677	response to antibiotic
GO:0051297	centrosome organization
GO:0051437	positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
GO:0051439	regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
GO:0051443	positive regulation of ubiquitin-protein transferase activity
GO:0051726	regulation of cell cycle
GO:0071168	protein localization to chromatin

Cellular Component

GO:0000776	kinetochore
GO:0000922	spindle pole
GO:0000942	condensed nuclear chromosome outer kinetochore
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005730	nucleolus
GO:0005737	cytoplasm
GO:0005813	centrosome
GO:0005819	spindle
GO:0005829	cytosol
GO:0005876	spindle microtubule
GO:0015630	microtubule cytoskeleton
GO:0030496	midbody
GO:0051233	spindle midzone

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR000959 POLO box duplicated domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF00659
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt