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Protein

Serine/threonine-protein kinase PLK4

Gene

Plk4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Phosphorylates CDC25C and CHEK2. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification (By similarity).By similarity2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei41ATPPROSITE-ProRule annotation1
Active sitei136Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi18 – 26ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • identical protein binding Source: IntAct
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • centriole replication Source: UniProtKB
  • de novo centriole assembly involved in multi-ciliated epithelial cell differentiation Source: UniProtKB
  • positive regulation of centriole replication Source: UniProtKB
  • protein phosphorylation Source: MGI
  • trophoblast giant cell differentiation Source: UniProtKB

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.21 3474
ReactomeiR-MMU-2565942 Regulation of PLK1 Activity at G2/M Transition
R-MMU-380259 Loss of Nlp from mitotic centrosomes
R-MMU-380270 Recruitment of mitotic centrosome proteins and complexes
R-MMU-380320 Recruitment of NuMA to mitotic centrosomes
R-MMU-5620912 Anchoring of the basal body to the plasma membrane
R-MMU-8854518 AURKA Activation by TPX2

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PLK4 (EC:2.7.11.21)
Alternative name(s):
Polo-like kinase 4
Short name:
PLK-4
Serine/threonine-protein kinase 18
Serine/threonine-protein kinase Sak
Gene namesi
Name:Plk4
Synonyms:Sak, Stk18
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:101783 Plk4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Disruption phenotypei

Death during embryogenesis. Embryos arrest after gastrulation at E7.5, with a marked increase in mitotic and apoptotic cells. Heterozygous mice are viable but show increased liver and lung cancers in elderly mice. Defects in heterozygous mice are associated with progressive cell cycle delays, increased spindle irregularities and accelerated hepatocellular carcinogenesis, probably due to increased centrosomal amplification, multipolar spindle formation and aneuploidy. The incidence of spontaneous.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi170T → D: Activating mutant. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000865681 – 925Serine/threonine-protein kinase PLK4Add BLAST925

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei45N6-acetyllysineBy similarity1
Modified residuei46N6-acetyllysineBy similarity1
Modified residuei400PhosphoserineBy similarity1
Modified residuei778PhosphoserineBy similarity1

Post-translational modificationi

Ubiquitinated; leading to its degradation by the proteasome.1 Publication
Tyrosine-phosphorylated by TEC.By similarity
Acetylation by KAT2A and KAT2B impairs kinase activity by shifting the kinase to an inactive conformation.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ64702
PRIDEiQ64702

PTM databases

iPTMnetiQ64702
PhosphoSitePlusiQ64702

Expressioni

Tissue specificityi

expressed in tissues associated with mitotic and meiotic cell division. Highly expressed in testis.1 Publication

Gene expression databases

BgeeiENSMUSG00000025758
CleanExiMM_PLK4
ExpressionAtlasiQ64702 baseline and differential
GenevisibleiQ64702 MM

Interactioni

Subunit structurei

Homodimer (PubMed:12352953). Interacts with CEP152 (via N-terminus) (By similarity). Interacts with CEP78; this interaction may be important for proper PLK4 localization to the centriole and PLK4-induced overduplication of centrioles (By similarity).By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi203545, 5 interactors
DIPiDIP-42244N
IntActiQ64702, 8 interactors
MINTiQ64702
STRINGi10090.ENSMUSP00000026858

Structurei

Secondary structure

1925
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi848 – 855Combined sources8
Beta strandi857 – 866Combined sources10
Beta strandi871 – 884Combined sources14
Beta strandi890 – 894Combined sources5
Helixi901 – 907Combined sources7
Turni908 – 910Combined sources3
Beta strandi913 – 917Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1MBYX-ray2.00A/B839-925[»]
ProteinModelPortaliQ64702
SMRiQ64702
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ64702

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 265Protein kinasePROSITE-ProRule annotationAdd BLAST254
Domaini847 – 911POLO boxPROSITE-ProRule annotationAdd BLAST65

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0575 Eukaryota
ENOG410XQBP LUCA
GeneTreeiENSGT00530000062954
HOVERGENiHBG053617
InParanoidiQ64702
KOiK08863
OMAiGADFEVW
OrthoDBiEOG091G05NQ
PhylomeDBiQ64702
TreeFamiTF101090

Family and domain databases

CDDicd13114 POLO_box_Plk4_1, 1 hit
cd13115 POLO_box_Plk4_2, 1 hit
cd13116 POLO_box_Plk4_3, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR033700 Plk4
IPR000959 POLO_box_dom
IPR033699 POLO_box_Plk4_1
IPR033698 POLO_box_Plk4_2
IPR033696 POLO_box_Plk4_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008266 Tyr_kinase_AS
PANTHERiPTHR24345:SF50 PTHR24345:SF50, 1 hit
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF00659 POLO_box, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50078 POLO_BOX, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q64702-1) [UniParc]FASTAAdd to basket
Also known as: Sak-a

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAACIGERIE DFKVGNLLGK GSFAGVYRAE SIHTGLEVAI KMIDKKAMYK
60 70 80 90 100
AGMVQRVQNE VKIHCQLKHP SVLELYNYFE DNNYVYLVLE MCHNGEMNRY
110 120 130 140 150
LKNRMKPFSE REARHFMHQI ITGMLYLHSH GILHRDLTLS NILLTRNMNI
160 170 180 190 200
KIADFGLATQ LNMPHEKHYT LCGTPNYISP EIATRSAHGL ESDIWSLGCM
210 220 230 240 250
FYTLLIGRPP FDTDTVKNTL NKVVLADYEM PAFLSREAQD LIHQLLRRNP
260 270 280 290 300
ADRLSLSSVL DHPFMSRNPS PKSKDVGTVE DSMDSGHATL STTITASSGT
310 320 330 340 350
SLSGSLLDRR LLVGQPLPNK ITVFQKNKNS SDFSSGDGSN FCTQWGNPEQ
360 370 380 390 400
EANSRGRGRV IEDAEERPHS RYLRRAHSSD RASPSNQSRA KTYSVERCHS
410 420 430 440 450
VEMLSKPRRS LDENQHSSNH HCLGKTPFPF ADQTPQMEMV QQWFGNLQMN
460 470 480 490 500
AHLGETNEHH TVSPNRDFQD YPDLQDTLRN AWTDTRASKN ADTSANVHAV
510 520 530 540 550
KQLSAMKYMS AHHHKPEVMP QEPGLHPHSE QSKNRSMEST LGYQKPTLRS
560 570 580 590 600
ITSPLIAHRL KPIRQKTKKA VVSILDSEEV CVELLRECAS EGYVKEVLQI
610 620 630 640 650
SSDGTMITVY YPNDGRGFPL ADRPPLPTDN ISRYSFDNLP EKYWRKYQYA
660 670 680 690 700
SRFIQLVRSK TPKITYFTRY AKCILMENSP GADFEVWFYD GAKIHKTENL
710 720 730 740 750
IHIIEKTGIS YNLKNENEVT SLKEEVKVYM DHANEGHRIC LSLESVISEE
760 770 780 790 800
EKRSRGSSFF PIIVGRKPGN TSSPKALSAP PVDPSCCKGE QASASRLSVN
810 820 830 840 850
SAAFPTQSPG LSPSTVTVEG LGHTATATGT GVSSSLPKSA QLLKSVFVKN
860 870 880 890 900
VGWATQLTSG AVWVQFNDGS QLVVQAGVSS ISYTSPDGQT TRYGENEKLP
910 920
EYIKQKLQCL SSILLMFSNP TPNFQ
Length:925
Mass (Da):103,746
Last modified:August 16, 2004 - v2
Checksum:iF28A64ED24D9C801
GO
Isoform 2 (identifier: Q64702-2) [UniParc]FASTAAdd to basket
Also known as: Sak-b

The sequence of this isoform differs from the canonical sequence as follows:
     417-464: SSNHHCLGKT...ETNEHHTVSP → RYSPTKSNVN...LLNLLNKFDR
     465-925: Missing.

Show »
Length:464
Mass (Da):52,718
Checksum:iBA676E303B37B55D
GO
Isoform 3 (identifier: Q64702-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     580-606: Missing.

Note: No experimental confirmation available.
Show »
Length:898
Mass (Da):100,805
Checksum:iC1FAAD17EE21A142
GO

Sequence cautioni

The sequence AAH51483 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti201F → S in AAC37648 (PubMed:8022793).Curated1
Sequence conflicti201F → S in AAC37649 (PubMed:8022793).Curated1
Sequence conflicti284D → E in BAB24759 (PubMed:16141072).Curated1
Sequence conflicti509M → V in BAB24599 (PubMed:16141072).Curated1
Sequence conflicti524G → D in AAH26785 (Ref. 3) Curated1
Sequence conflicti524G → D in AAH57940 (Ref. 3) Curated1
Sequence conflicti589A → E in AAH26785 (Ref. 3) Curated1
Sequence conflicti629D → N in AAH26785 (Ref. 3) Curated1
Sequence conflicti629D → N in AAH57940 (Ref. 3) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011369417 – 464SSNHH…HTVSP → RYSPTKSNVNVLTSLNTKQP IVKDLLKDRIMTEQYKDNLL NLLNKFDR in isoform 2. 1 PublicationAdd BLAST48
Alternative sequenceiVSP_011370465 – 925Missing in isoform 2. 1 PublicationAdd BLAST461
Alternative sequenceiVSP_011371580 – 606Missing in isoform 3. 1 PublicationAdd BLAST27

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L29479 mRNA Translation: AAC37648.1
L29480 mRNA Translation: AAC37649.1
AK006459 mRNA Translation: BAB24599.1
AK006827 mRNA Translation: BAB24759.1
AK137080 mRNA Translation: BAE23231.1
AK137471 mRNA Translation: BAE23367.1
CH466530 Genomic DNA Translation: EDL35140.1
CH466530 Genomic DNA Translation: EDL35142.1
BC026785 mRNA Translation: AAH26785.1
BC051483 mRNA Translation: AAH51483.1 Different initiation.
BC057940 mRNA Translation: AAH57940.1
CCDSiCCDS17328.1 [Q64702-1]
CCDS57210.1 [Q64702-3]
PIRiA55748
RefSeqiNP_035625.2, NM_011495.2 [Q64702-1]
NP_775261.2, NM_173169.2 [Q64702-3]
UniGeneiMm.3794

Genome annotation databases

EnsembliENSMUST00000026858; ENSMUSP00000026858; ENSMUSG00000025758 [Q64702-1]
ENSMUST00000203295; ENSMUSP00000145277; ENSMUSG00000025758 [Q64702-3]
GeneIDi20873
KEGGimmu:20873
UCSCiuc008pbm.1 mouse [Q64702-2]
uc008pbo.1 mouse [Q64702-1]
uc012cpc.1 mouse [Q64702-3]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPLK4_MOUSE
AccessioniPrimary (citable) accession number: Q64702
Secondary accession number(s): Q3UVA3
, Q6PEP6, Q78EG6, Q80UT6, Q8R0I5, Q9CVR6, Q9CVU6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: August 16, 2004
Last modified: May 23, 2018
This is version 158 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families

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