ID:PLK1_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein kinase PLK1; EC=2.7.11.21; AltName: Full=Polo-like kinase 1; Short=PLK-1; AltName: Full=Serine/threonine-protein kinase 13; Short=STPK13; 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, MLF1IP, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, PLK1S1/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 PLK1S1/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, MLF1IP, 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, MLF1IP, 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 chromatide 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. 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. SUBUNIT: Interacts with CEP170 and EVI5. Interacts and phosphorylates ERCC6L. Interacts with FAM29A. Interacts with SLX4/BTBD12 and TTDN1. Interacts with BUB1B. Interacts (via POLO- box domain) with the phosphorylated form of BUB1, MLF1IP and CDC25C. Interacts with isoform 3 of SGOL1. Interacts with BORA, KIF2A and AURKA. Interacts with TOPORS and CYLD. Interacts with ECT2; the interaction is stimulated upon phosphorylation of ECT2 on 'Thr-444'. Interacts with PRC1. Interacts with KIF20A/MKLP2 (when phosphorylated), leading to the recruitment at the central spindle. Interacts (via POLO box domains) with PPP1R12A/MYPT1 (when previously phosphorylated by CDK1). Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing SKAP, SPAG5, PLK1, DYNLL1 and SGOL2. Interacts with BIRC6/bruce. Interacts with CDK1- phosphorylated FRY; this interaction occurs in mitotic cells, but not in interphase cells. FRY interaction facilitates AURKA- mediated PLK1 phosphorylation. INTERACTION: Q9NR09:BIRC6; NbExp=3; IntAct=EBI-476768, EBI-1765160; O96017:CHEK2; NbExp=6; IntAct=EBI-476768, EBI-1180783; P23588:EIF4B; NbExp=3; IntAct=EBI-476768, EBI-970310; O60447:EVI5; NbExp=2; IntAct=EBI-476768, EBI-852291; Q13158:FADD; NbExp=9; IntAct=EBI-476768, EBI-494804; P08107:HSPA1B; NbExp=5; IntAct=EBI-476768, EBI-629985; P33993:MCM7; NbExp=4; IntAct=EBI-476768, EBI-355924; O75665:OFD1; NbExp=2; IntAct=EBI-476768, EBI-716327; Q8IXK0:PHC2; NbExp=2; IntAct=EBI-476768, EBI-713786; Q8IY92:SLX4; NbExp=6; IntAct=EBI-476768, EBI-2370740; Q92844:TANK; NbExp=3; IntAct=EBI-476768, EBI-356349; SUBCELLULAR LOCATION: Nucleus. Chromosome, centromere, kinetochore. Cytoplasm, cytoskeleton, 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. TISSUE SPECIFICITY: Placenta and colon. DEVELOPMENTAL STAGE: Accumulates to a maximum during the G2 and M phases, declines to a nearly undetectable level following mitosis and throughout G1 phase, and then begins to accumulate again during S phase. INDUCTION: By growth-stimulating agents. DOMAIN: The POLO box domains act as phosphopeptide-binding module that recongnize and bind serine-[phosphothreonine/phosphoserine]- (proline/X) motifs. PLK1 recognizes and binds docking proteins that are already phosphorylated on these motifs, and then phosphorylates them. PLK1 can also create its own docking sites by mediating phosphorylation of serine- [phosphothreonine/phosphoserine]-(proline/X) motifs subsequently recognized by the POLO box domains. PTM: 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 and gradually disappears from centrosomes during anaphase. Dephosphorylation at Thr-210 at centrosomes is probably mediated by protein phosphatase 1C (PP1C), via interaction with PPP1R12A/MYPT1. Autophosphorylation and 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. Phosphorylated in vitro by STK10. PTM: Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) in anaphase and following DNA damage, leading to its degradation by the proteasome. Ubiquitination is mediated via its interaction with FZR1/CDH1. Ubiquitination and subsequent degradation prevents entry into mitosis and is essential to maintain an efficient G2 DNA damage checkpoint. DISEASE: Note=Defects in PLK1 are associated with some cancers, such as gastric, thyroid or B-cel lymphomas. Expression is cancer increased in tumor tissues with a poor prognosis, suggesting a role in malignant transformations and carcinogenesis. SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily. SIMILARITY: Contains 2 POLO box domains. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PLK1ID41747ch16p12.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00069 - Protein kinase domain PF00659 - POLO box duplicated region PF07714 - Protein tyrosine and serine/threonine kinase PF14531 - Kinase-like PF17667 - Fungal protein kinase
ModBase Predicted Comparative 3D Structure on P53350
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BioCarta from NCI Cancer Genome Anatomy Project h_g2Pathway - Cell Cycle: G2/M Checkpoint
Reactome (by CSHL, EBI, and GO)
Protein P53350 (Reactome details) participates in the following event(s):
R-HSA-3002811 Myosin phosphatase dephosphorylates PLK1 R-HSA-380311 Recruitment of Plk1 to centrosomes R-NUL-2423781 PLK1 binds phosphorylated Gorasp1 R-HSA-3000319 BORA binds PLK1 and AURKA R-HSA-2172194 Recruitment of PLK1 to phosphorylated GORASP1 (GRASP65) R-HSA-3002798 Cytosolic PLK1 translocates to the nucleus R-HSA-8852324 GTSE1 binds PLK1 R-HSA-3000327 PLK1 phosphorylates BORA R-HSA-8852317 PLK1 phosphorylates GTSE1 R-HSA-2294590 PLK1 binds phosphorylated condensin II complex R-HSA-4088130 PLK1 binds FOXM1 R-HSA-4088134 PLK1 phosphorylates FOXM1 R-HSA-141409 Mad1 binds kinetochore R-HSA-375302 Kinetochore capture of astral microtubules R-HSA-5666129 CDC42:GTP recruits DIAPH2-2 to kinetochores R-HSA-5666169 Kinetochore capture of astral microtubules is positively regulated by CDC42:GTP:p-S196-DIAPH2-2 R-HSA-380272 Plk1-mediated phosphorylation of Nlp R-HSA-380283 Recruitment of additional gamma tubulin/ gamma TuRC to the centrosome R-HSA-380294 Loss of C-Nap-1 from centrosomes R-HSA-380455 Recruitment of CDK11p58 to the centrosomes R-HSA-380303 Dissociation of Phospho-Nlp from the centrosome R-HSA-5626220 C2CD3 binds the mother centriole R-HSA-174088 Association of cell cycle proteins with the APC/C:Cdh1 complex R-HSA-1638803 Phosphorylation of cohesin by PLK1 at centromeres R-HSA-2466068 Phosphorylation of cohesin by PLK1 at chromosomal arms R-HSA-2214351 PLK1 phosphorylates GORASP1 R-HSA-3000310 AURKA phosphorylates PLK1 R-HSA-156678 Activation of Cdc25C R-HSA-2562526 PLK1 phosphorylates OPTN R-HSA-2984226 PLK1 phosphorylates NEK9 R-HSA-2294580 PLK1 hyperphosphorylates Condensin II complex R-HSA-156673 Regulation of KIF23 (MKLP1) by phosphorylation R-HSA-156682 Regulation of NUDC by phosphorylation R-HSA-156699 Inactivation of Wee1 kinase R-HSA-156723 Regulation of KIF20A (MKL2) by phosphorylation R-HSA-162657 Inactivation of Myt1 kinase R-HSA-163010 Down Regulation of Emi1 through Phosphorylation of Emi1 R-HSA-174119 Free APC/C phosphorylated by Plk1 R-HSA-174174 Phosphorylation of the Emi1 DSGxxS degron by Plk1 R-HSA-141431 MAD2 associates with the Mad1 kinetochore complex R-HSA-141439 Release of activated MAD2 from kinetochores R-HSA-2467811 Separation of sister chromatids R-HSA-2467809 ESPL1 (Separase) cleaves centromeric cohesin R-HSA-5666160 AURKB phosphorylates DIAPH2-2 at kinetochores R-HSA-380508 Translocation of NuMA to the centrosomes R-HSA-2574845 AJUBA binds centrosome-associated AURKA R-HSA-8853405 TPX2 binds AURKA at centrosomes R-HSA-2574840 AJUBA facilitates AURKA autophosphorylation R-HSA-5626223 C2CD3 and OFD1 recruit 5 distal appendage proteins to the centriole R-HSA-5626681 Recruitment of transition zone proteins R-HSA-5626227 CP110 and CEP97 dissociate from the centriole R-HSA-174195 Ubiquitination of cell cycle proteins targeted by the APC/C:Cdh1complex R-HSA-170126 Phosphorylation of Cyclin B1 in the CRS domain R-HSA-141422 MAD2 converted to an inhibitory state via interaction with Mad1 R-HSA-1638821 PP2A-B56 dephosphorylates centromeric cohesin R-HSA-2468287 CDK1 phosphorylates CDCA5 (Sororin) at centromeres R-HSA-380316 Association of NuMA with microtubules R-HSA-8853419 TPX2 promotes AURKA autophosphorylation R-HSA-5626228 The distal appendage proteins recruit TTBK2 R-HSA-5638009 CEP164 recruits RAB3IP-carrying Golgi-derived vesicles to the basal body R-HSA-5626699 MARK4 binds ODF2 in the centriole R-HSA-5617816 RAB3IP stimulates nucleotide exchange on RAB8A R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes R-HSA-156711 Polo-like kinase mediated events R-HSA-162658 Golgi Cisternae Pericentriolar Stack Reorganization R-HSA-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint R-HSA-2299718 Condensation of Prophase Chromosomes R-HSA-69275 G2/M Transition R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal R-HSA-68877 Mitotic Prometaphase R-HSA-5663220 RHO GTPases Activate Formins R-HSA-380259 Loss of Nlp from mitotic centrosomes R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centrosome R-HSA-5620912 Anchoring of the basal body to the plasma membrane R-HSA-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 R-HSA-380287 Centrosome maturation R-HSA-2500257 Resolution of Sister Chromatid Cohesion R-HSA-68875 Mitotic Prophase R-HSA-2562597 Optineurin and Myosin Phosphatase Negatively Regulate PLK1 R-HSA-2980767 Activation of NIMA Kinases NEK9, NEK6, NEK7 R-HSA-68884 Mitotic Telophase/Cytokinesis R-HSA-68881 Mitotic Metaphase/Anaphase Transition R-HSA-176412 Phosphorylation of the APC/C R-HSA-176417 Phosphorylation of Emi1 R-HSA-453274 Mitotic G2-G2/M phases R-HSA-2467813 Separation of Sister Chromatids R-HSA-141424 Amplification of signal from the kinetochores R-HSA-68886 M Phase R-HSA-195258 RHO GTPase Effectors R-HSA-380320 Recruitment of NuMA to mitotic centrosomes R-HSA-8854518 AURKA Activation by TPX2 R-HSA-5617833 Cilium Assembly R-HSA-174143 APC/C-mediated degradation of cell cycle proteins R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition R-HSA-2980766 Nuclear Envelope Breakdown R-HSA-2555396 Mitotic Metaphase and Anaphase R-HSA-176814 Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase R-HSA-69278 Cell Cycle (Mitotic) R-HSA-68882 Mitotic Anaphase R-HSA-69618 Mitotic Spindle Checkpoint R-HSA-194315 Signaling by Rho GTPases R-HSA-1852241 Organelle biogenesis and maintenance R-HSA-453276 Regulation of mitotic cell cycle R-HSA-1640170 Cell Cycle R-HSA-69620 Cell Cycle Checkpoints R-HSA-162582 Signal Transduction
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Common Gene Haplotype Alleles 
