PLK1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: PLK1_MOUSE
• UniProt AC: Q07832
• Protein Name: Serine/threonine-protein kinase PLK1
• Gene Name: Plk1
• Organism: Mus musculus (Mouse).
• Sequence Length: 603
• Subcellular Localization: Nucleus . Chromosome, centromere, kinetochore . Cytoplasm, cytoskeleton, microtubule organizing center, centrosome . Cytoplasm, cytoskeleton, spindle . Midbody . localization at the centrosome starts at the G1/S transition (By similarity). During ear
• Protein Description: 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 (By similarity). 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. [PubMed: 25533956 Phosphorylates CEP68 and is required for its degradation. Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope (By similarity Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock (By similarity 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 (By similarity Regulates mitotic progression by phosphorylating RIOK2 (By similarity]
• Protein Sequence: MNAAAKAGKLARAPADLGKGGVPGDAVPGAPVAAPLAKEIPEVLVDPRSRRQYVRGRFLGKGGFAKCFEISDADTKEVFAGKIVPKSLLLKPHQKEKMSMEISIHRSLAHQHVVGFHDFFEDSDFVFVVLELCRRRSLLELHKRRKALTEPEARYYLRQIVLGCQYLHRNQVIHRDLKLGNLFLNEDLEVKIGDFGLATKVEYEGERKKTLCGTPNYIAPEVLSKKGHSFEVDVWSIGCIMYTLLVGKPPFETSCLKETYLRIKKNEYSIPKHINPVAASLIQKMLQTDPTARPTIHELLNDEFFTSGYIPARLPITCLTIPPRFSIAPSSLDPSSRKPLKVLNKGVENPLPDRPREKEEPVVRETNEAIECHLSDLLQQLTSVNASKPSERGLVRQEEAEDPACIPIFWVSKWVDYSDKYGLGYQLCDNSVGVLFNDSTRLILYNDGDSLQYIERDGTESYLTVSSHPNSLMKKITLLNYFRNYMSEHLLKAGANITPREGDELARLPYLRTWFRTRSAIILHLSNGTVQINFFQDHTKLILCPLMAAVTYINEKRDFQTYRLSLLEEYGCCKELASRLRYARTMVDKLLSSRSASNRLKAS

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
103	Phosphorylation	EKMSMEISIHRSLAH HCCCEEEEHHHHHHH	10.07	-
137	Phosphorylation	LELCRRRSLLELHKR HHHHHHHHHHHHHHH	35.18	-
166	Phosphorylation	QIVLGCQYLHRNQVI HHHHHCHHHCCCCEE	14.46	-
210	Phosphorylation	YEGERKKTLCGTPNY EECCCCCCCCCCCCC	30.25	22322096
214	Phosphorylation	RKKTLCGTPNYIAPE CCCCCCCCCCCCCHH	13.83	25619855
269	Phosphorylation	RIKKNEYSIPKHINP HHHCCCCCCCCCCCH	26.66	-
326	Phosphorylation	LTIPPRFSIAPSSLD EECCCCCCCCCCCCC	21.08	28066266
330	Phosphorylation	PRFSIAPSSLDPSSR CCCCCCCCCCCCCCC	34.21	28066266
331	Phosphorylation	RFSIAPSSLDPSSRK CCCCCCCCCCCCCCC	35.41	28066266
335	Phosphorylation	APSSLDPSSRKPLKV CCCCCCCCCCCCCCH	42.30	28066266
336	Phosphorylation	PSSLDPSSRKPLKVL CCCCCCCCCCCCCHH	50.11	28066266
375	Phosphorylation	EAIECHLSDLLQQLT HHHHHHHHHHHHHHH	11.53	-
445	Phosphorylation	DSTRLILYNDGDSLQ CCCEEEEECCCCCEE	12.29	-
450	Phosphorylation	ILYNDGDSLQYIERD EEECCCCCEEEEEEC	23.93	-
498	Phosphorylation	LKAGANITPREGDEL HHCCCCCCCCCCCHH	18.99	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
166	Y	Phosphorylation	Kinase	SRC	P12931	PSP
210	T	Phosphorylation	Kinase	AURKA	P97477	Uniprot
445	Y	Phosphorylation	Kinase	SRC	P12931	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	Chfr	Q810L3	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
137	S	Phosphorylation	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.	-
210	T	Phosphorylation	Catalytic activity is enhanced by phosphorylation of Thr-210.	9154840
210	T	Phosphorylation	Dephosphorylation at Thr-210 at centrosomes is probably mediated by protein phosphatase 1C (PP1C), via interaction with PPP1R12A/MYPT1.	9154840
210	T	Phosphorylation	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.	9154840
492	K	ubiquitylation	Monoubiquitination at Lys-492 by the BCR(KLHL22) ubiquitin ligase complex does not lead to degradation: it promotes PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation (By similarity).	-

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of PLK1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PRRC1_HUMAN	PRRC1	physical	20360068
NU214_HUMAN	NUP214	physical	20360068
ERC6L_HUMAN	ERCC6L	physical	20360068
SKAP_HUMAN	KNSTRN	physical	20360068
RGPD8_HUMAN	RGPD8	physical	20360068
HAUS8_HUMAN	HAUS8	physical	20360068
TARA_HUMAN	TRIOBP	physical	20360068
NSUN2_HUMAN	NSUN2	physical	20360068
STXB4_HUMAN	STXBP4	physical	20360068
BORA_HUMAN	BORA	physical	20360068
KIF24_HUMAN	KIF24	physical	20360068
JIP4_HUMAN	SPAG9	physical	20360068
RAI14_HUMAN	RAI14	physical	20360068
SPAG5_HUMAN	SPAG5	physical	20360068
TOPB1_HUMAN	TOPBP1	physical	20360068
CEP97_HUMAN	CEP97	physical	20360068
RAGP1_HUMAN	RANGAP1	physical	20360068
RBP2_HUMAN	RANBP2	physical	20360068
HAUS1_HUMAN	HAUS1	physical	20360068
SUMO1_HUMAN	SUMO1	physical	20360068
BICD2_HUMAN	BICD2	physical	20360068
SLX4_HUMAN	SLX4	physical	20360068
PLK1_HUMAN	PLK1	physical	20360068
PRC1_HUMAN	PRC1	physical	20360068
WDCP_HUMAN	C2orf44	physical	20360068
DX39B_MOUSE	Ddx39b	physical	21637952
SRBP1_HUMAN	SREBF1	physical	27579997

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.