DegronMD - P53350(PLK1)

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, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 and HNRNPU. 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 SGO1: required for spindle pole localization of isoform 3 of SGO1 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). Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope (PubMed:20679239). Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock (PubMed:15661742). Phosphorylates HSF1 also in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex induicing HSF1 degradation, and hence mitotic progression (PubMed:18794143). Regulates mitotic progression by phosphorylating RIOK2 (PubMed:21880710). Through the phosphorylation of DZIP1 regulates the localization during mitosis of the BBSome, a ciliary protein complex involved in cilium biogenesis (PubMed:27979967). {ECO:0000250|UniProtKB:Q5F2C3, ECO:0000269|PubMed:11202906, ECO:0000269|PubMed:12207013, ECO:0000269|PubMed:12447691, ECO:0000269|PubMed:12524548, ECO:0000269|PubMed:12738781, ECO:0000269|PubMed:12852856, ECO:0000269|PubMed:12939256, ECO:0000269|PubMed:14532005, ECO:0000269|PubMed:14734534, ECO:0000269|PubMed:15070733, ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984, ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:16198290, ECO:0000269|PubMed:16247472, ECO:0000269|PubMed:16980960, ECO:0000269|PubMed:17081991, ECO:0000269|PubMed:17351640, ECO:0000269|PubMed:17376779, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:18174154, ECO:0000269|PubMed:18331714, ECO:0000269|PubMed:18418051, ECO:0000269|PubMed:18477460, ECO:0000269|PubMed:18521620, ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:19160488, ECO:0000269|PubMed:19351716, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:19473992, ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19597481, ECO:0000269|PubMed:20679239, ECO:0000269|PubMed:21880710, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23509069, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25986610, ECO:0000269|PubMed:27979967, ECO:0000269|PubMed:8991084}. 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GO - Biological processes (BP): centrosome cycle [GO:0007098]; establishment of mitotic spindle orientation [GO:0000132]; establishment of protein localization [GO:0045184]; female meiosis chromosome segregation [GO:0016321]; G2/M transition of mitotic cell cycle [GO:0000086]; homologous chromosome segregation [GO:0045143]; microtubule bundle formation [GO:0001578]; mitotic cell cycle [GO:0000278]; mitotic chromosome condensation [GO:0007076]; mitotic cytokinesis [GO:0000281]; mitotic G2 DNA damage checkpoint signaling [GO:0007095]; mitotic nuclear membrane disassembly [GO:0007077]; mitotic sister chromatid segregation [GO:0000070]; mitotic spindle assembly checkpoint signaling [GO:0007094]; mitotic spindle organization [GO:0007052]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cyclin-dependent protein serine/threonine kinase activity [GO:0045736]; negative regulation of transcription by RNA polymerase II [GO:0000122]; nuclear membrane disassembly [GO:0051081]; peptidyl-serine phosphorylation [GO:0018105]; positive regulation of peptidyl-threonine phosphorylation [GO:0010800]; positive regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032436]; positive regulation of protein localization to nucleus [GO:1900182]; positive regulation of proteolysis [GO:0045862]; positive regulation of ubiquitin protein ligase activity [GO:1904668]; positive regulation of ubiquitin-protein transferase activity [GO:0051443]; protein destabilization [GO:0031648]; protein localization to chromatin [GO:0071168]; protein localization to nuclear envelope [GO:0090435]; protein phosphorylation [GO:0006468]; protein ubiquitination [GO:0016567]; regulation of anaphase-promoting complex-dependent catabolic process [GO:1905784]; regulation of cell cycle [GO:0051726]; regulation of cytokinesis [GO:0032465]; regulation of mitotic cell cycle [GO:0007346]; regulation of mitotic cell cycle phase transition [GO:1901990]; regulation of mitotic metaphase/anaphase transition [GO:0030071]; regulation of mitotic spindle assembly [GO:1901673]; regulation of protein binding [GO:0043393]; regulation of protein localization to cell cortex [GO:1904776]; sister chromatid cohesion [GO:0007062]; synaptonemal complex disassembly [GO:0070194] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S335C	TCGA-38-4625	LUAD	TCGA	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.75
p.S335C	DO23952	LUAD	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.75
p.S326L	TCGA-3N-A9WC	SKCM	TCGA	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.5
p.S326L	TCGA-AG-A002	READ	TCGA	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.5
p.S326L	TCGA-AP-A1DV	UCEC	TCGA	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.5
p.S326L	TCGA-EE-A3JB	SKCM	TCGA	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.5
p.S326L	TCGA-ER-A2NH	SKCM	TCGA	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.5
p.S326L	DO222884	COCA	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.5
p.S326L	DO222696	MELA	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.5
p.S326L	DO47683	SKCM	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.5
p.S326L	DO51250	SKCM	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.5
p.S326L	DO51234	SKCM	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.5
p.S326L	DO43186	UCEC	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.5
p.S326L	SIDM01611	Endometrial Carcinoma	GDSC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.5
p.S326L	ACH-000996	Endometrial/Uterine Cancer	CCLE	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.5
p.R337W	TCGA-A5-A0G1	UCEC	TCGA	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation altering degron motif	0.8634
p.R337W	TCGA-BR-4280	STAD	TCGA	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation altering degron motif	0.8634
p.R337W	DO227686	COCA	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation altering degron motif	0.8634
p.R337W	DO38663	STAD	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation altering degron motif	0.8634
p.R337W	DO42472	UCEC	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation altering degron motif	0.8634
p.T341I	TCGA-A5-A0GA	UCEC	TCGA	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation altering degron motif	0.7078
p.T341I	DO43763	UCEC	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation altering degron motif	0.7078
p.R441C	TCGA-AX-A1C9	UCEC	TCGA	RLILYND	LIG_APCC_ABBAyCdc20_2	441:447	Mutation altering degron motif	0.8301
p.R441C	DO43098	UCEC	ICGC	RLILYND	LIG_APCC_ABBAyCdc20_2	441:447	Mutation altering degron motif	0.8301
p.R441C	SIDM00217	Colorectal Carcinoma	GDSC	RLILYND	LIG_APCC_ABBAyCdc20_2	441:447	Mutation altering degron motif	0.8301
p.R441C	ACH-000999	Colon/Colorectal Cancer	CCLE	RLILYND	LIG_APCC_ABBAyCdc20_2	441:447	Mutation altering degron motif	0.8301
p.R441C	SNU-1040	large intestine	COSMIC	RLILYND	LIG_APCC_ABBAyCdc20_2	441:447	Mutation altering degron motif	0.8301
p.R456C	TCGA-DK-A6AW	BLCA	TCGA	RLILYND	LIG_APCC_ABBAyCdc20_2	441:447	Mutation rewiring degron network	0.0833
p.R456C	DO48566	BLCA	ICGC	RLILYND	LIG_APCC_ABBAyCdc20_2	441:447	Mutation rewiring degron network	0.0833
p.R456C	DO229211	THCA	ICGC	RLILYND	LIG_APCC_ABBAyCdc20_2	441:447	Mutation rewiring degron network	0.0833
p.V342F	TCGA-EO-A22U	UCEC	TCGA	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation altering degron motif	0.5957
p.V342F	DO43755	UCEC	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation altering degron motif	0.5957
p.D457G	TCGA-NH-A5IV	COAD	TCGA	RLILYND	LIG_APCC_ABBAyCdc20_2	441:447	Mutation rewiring degron network	0.0556
p.D457G	DO49095	COAD	ICGC	RLILYND	LIG_APCC_ABBAyCdc20_2	441:447	Mutation rewiring degron network	0.0556
p.R354C	TCGA-VQ-A91K	STAD	TCGA	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation rewiring degron network	0.0556
p.R354C	DO51785	STAD	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation rewiring degron network	0.0556
p.R456H	TCGA-XK-AAIW	PRAD	TCGA	RLILYND	LIG_APCC_ABBAyCdc20_2	441:447	Mutation rewiring degron network	0.0833
p.R456H	DO51407	PRAD	ICGC	RLILYND	LIG_APCC_ABBAyCdc20_2	441:447	Mutation rewiring degron network	0.0833
p.R354H	DO230346	COCA	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation rewiring degron network	0.0556
p.R354H	DO227979	COCA	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation rewiring degron network	0.0556
p.R354H	DO233168	GACA	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation rewiring degron network	0.0556
p.R354H	SIDM00611	Kidney Carcinoma	GDSC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation rewiring degron network	0.0556
p.R354H	SIDM00486	Squamous Cell Lung Carcinoma	GDSC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation rewiring degron network	0.0556
p.R354H	SIDM00214	Colorectal Carcinoma	GDSC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation rewiring degron network	0.0556
p.R354H	SIDM00549	B-Lymphoblastic Leukemia	GDSC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation rewiring degron network	0.0556
p.R354H	EBC-1	lung	COSMIC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation rewiring degron network	0.0556
p.R354H	LC4-1	haematopoietic and lymphoid tissue	COSMIC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation rewiring degron network	0.0556
p.R354H	KMRC-1	kidney	COSMIC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation rewiring degron network	0.0556
p.R354H	SNU-407	large intestine	COSMIC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation rewiring degron network	0.0556
p.D333Y	DO228948	LICA	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation rewiring degron network	0.25
p.I327V	DO229061	LICA	ICGC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation rewiring degron network	0.0833
p.S335R	ACH-000398	Lymphoma	CCLE	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.75
p.S335R	ACH-001022	Bone Cancer	CCLE	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.75
p.S335R	ACH-001454	Colon/Colorectal Cancer	CCLE	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.75
p.S335R	ACH-002144	Lung Cancer	CCLE	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.75
p.S335R	IST-SL1	lung	COSMIC	NRKPLTVLN	DEG_APCC_DBOX_1	336:344	Mutation blocking phosphorylation signal	0.75

Kaplan plot for PLK1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

PLK1

UniProt ID: P53350

Entrez ID: 5347

Protein name: Serine/threonine-protein kinase PLK1 (EC 2.7.11.21) (Polo-like kinase 1) (PLK-1) (Serine/threonine-protein kinase 13) (STPK13)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PLK1 in