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Q64702 (PLK4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Plk4
Synonyms:Sak, Stk18
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length925 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.9

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subunit structure

Homodimer. Interacts with CEP152 (via N-terminus) By similarity. Ref.10

Subcellular location

Cytoplasmcytoskeletonmicrotubule organizing centercentrosomecentriole. Nucleusnucleolus. Cleavage furrow. Note: Associates with centrioles throughout the cell cycle. According to Ref.6, it localizes to the nucleolus during G2, to the centrosomes in G2/M, and to the cleavage furrow during cytokinesis. Component of the deuterosome, a structure that promotes de novo centriole amplification in multiciliated cells that can generate more than 100 centrioles. Ref.6 Ref.8 Ref.9 Ref.10

Tissue specificity

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

Post-translational modification

Ubiquitinated; leading to its degradation by the proteasome. Ref.5

Tyrosine-phosphorylated by TEC By similarity.

Disruption phenotype

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. Ref.6 Ref.7

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily.

Contains 1 POLO box domain.

Contains 1 protein kinase domain.

Sequence caution

The sequence AAH51483.1 differs from that shown. Reason: Erroneous initiation.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself4EBI-2552433,EBI-2552433
P037722EBI-2552433,EBI-4478820From a different organism.
CCNB3Q8WWL74EBI-2552433,EBI-767764From a different organism.
MBPP02686-12EBI-2552433,EBI-7056012From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q64702-1)

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.
Isoform 2 (identifier: Q64702-2)

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.
Isoform 3 (identifier: Q64702-3)

The sequence of this isoform differs from the canonical sequence as follows:
     580-606: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 925925Serine/threonine-protein kinase PLK4
PRO_0000086568

Regions

Domain12 – 265254Protein kinase
Domain847 – 91165POLO box
Nucleotide binding18 – 269ATP By similarity

Sites

Active site1361Proton acceptor By similarity
Binding site411ATP By similarity

Amino acid modifications

Modified residue4001Phosphoserine By similarity
Modified residue7781Phosphoserine By similarity

Natural variations

Alternative sequence417 – 46448SSNHH…HTVSP → RYSPTKSNVNVLTSLNTKQP IVKDLLKDRIMTEQYKDNLL NLLNKFDR in isoform 2.
VSP_011369
Alternative sequence465 – 925461Missing in isoform 2.
VSP_011370
Alternative sequence580 – 60627Missing in isoform 3.
VSP_011371

Experimental info

Mutagenesis1701T → D: Activating mutant. Ref.8
Sequence conflict2011F → S in AAC37648. Ref.1
Sequence conflict2011F → S in AAC37649. Ref.1
Sequence conflict2841D → E in BAB24759. Ref.2
Sequence conflict5091M → V in BAB24599. Ref.2
Sequence conflict5241G → D in AAH26785. Ref.3
Sequence conflict5241G → D in AAH57940. Ref.3
Sequence conflict5891A → E in AAH26785. Ref.3
Sequence conflict6291D → N in AAH26785. Ref.3
Sequence conflict6291D → N in AAH57940. Ref.3

Secondary structure

.............. 925
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Sak-a) [UniParc].

Last modified August 16, 2004. Version 2.
Checksum: F28A64ED24D9C801

FASTA925103,746
        10         20         30         40         50         60 
MAACIGERIE DFKVGNLLGK GSFAGVYRAE SIHTGLEVAI KMIDKKAMYK AGMVQRVQNE 

        70         80         90        100        110        120 
VKIHCQLKHP SVLELYNYFE DNNYVYLVLE MCHNGEMNRY LKNRMKPFSE REARHFMHQI 

       130        140        150        160        170        180 
ITGMLYLHSH GILHRDLTLS NILLTRNMNI KIADFGLATQ LNMPHEKHYT LCGTPNYISP 

       190        200        210        220        230        240 
EIATRSAHGL ESDIWSLGCM FYTLLIGRPP FDTDTVKNTL NKVVLADYEM PAFLSREAQD 

       250        260        270        280        290        300 
LIHQLLRRNP ADRLSLSSVL DHPFMSRNPS PKSKDVGTVE DSMDSGHATL STTITASSGT 

       310        320        330        340        350        360 
SLSGSLLDRR LLVGQPLPNK ITVFQKNKNS SDFSSGDGSN FCTQWGNPEQ EANSRGRGRV 

       370        380        390        400        410        420 
IEDAEERPHS RYLRRAHSSD RASPSNQSRA KTYSVERCHS VEMLSKPRRS LDENQHSSNH 

       430        440        450        460        470        480 
HCLGKTPFPF ADQTPQMEMV QQWFGNLQMN AHLGETNEHH TVSPNRDFQD YPDLQDTLRN 

       490        500        510        520        530        540 
AWTDTRASKN ADTSANVHAV KQLSAMKYMS AHHHKPEVMP QEPGLHPHSE QSKNRSMEST 

       550        560        570        580        590        600 
LGYQKPTLRS ITSPLIAHRL KPIRQKTKKA VVSILDSEEV CVELLRECAS EGYVKEVLQI 

       610        620        630        640        650        660 
SSDGTMITVY YPNDGRGFPL ADRPPLPTDN ISRYSFDNLP EKYWRKYQYA SRFIQLVRSK 

       670        680        690        700        710        720 
TPKITYFTRY AKCILMENSP GADFEVWFYD GAKIHKTENL IHIIEKTGIS YNLKNENEVT 

       730        740        750        760        770        780 
SLKEEVKVYM DHANEGHRIC LSLESVISEE EKRSRGSSFF PIIVGRKPGN TSSPKALSAP 

       790        800        810        820        830        840 
PVDPSCCKGE QASASRLSVN SAAFPTQSPG LSPSTVTVEG LGHTATATGT GVSSSLPKSA 

       850        860        870        880        890        900 
QLLKSVFVKN VGWATQLTSG AVWVQFNDGS QLVVQAGVSS ISYTSPDGQT TRYGENEKLP 

       910        920 
EYIKQKLQCL SSILLMFSNP TPNFQ 

« Hide

Isoform 2 (Sak-b) [UniParc].

Checksum: BA676E303B37B55D
Show »

FASTA46452,718
Isoform 3 [UniParc].

Checksum: C1FAAD17EE21A142
Show »

FASTA898100,805

References

« Hide 'large scale' references
[1]"Sak, a murine protein-serine/threonine kinase that is related to the Drosophila polo kinase and involved in cell proliferation."
Fode C., Motro B., Yousefi S., Heffernan M., Dennis J.W.
Proc. Natl. Acad. Sci. U.S.A. 91:6388-6392(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
Strain: DBA/2.
Tissue: Lymphoma.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Strain: C57BL/6J.
Tissue: Bone, Embryo and Testis.
[3]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
Strain: FVB/N.
Tissue: Mammary tumor.
[5]"Constitutive expression of murine Sak-a suppresses cell growth and induces multinucleation."
Fode C., Binkert C., Dennis J.W.
Mol. Cell. Biol. 16:4665-4672(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION.
[6]"Late mitotic failure in mice lacking Sak, a polo-like kinase."
Hudson J.W., Kozarova A., Cheung P., Macmillan J.C., Swallow C.J., Cross J.C., Dennis J.W.
Curr. Biol. 11:441-446(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
[7]"Plk4 haploinsufficiency causes mitotic infidelity and carcinogenesis."
Ko M.A., Rosario C.O., Hudson J.W., Kulkarni S., Pollett A., Dennis J.W., Swallow C.J.
Nat. Genet. 37:883-888(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[8]"Nucleolar release of Hand1 acts as a molecular switch to determine cell fate."
Martindill D.M.J., Risebro C.A., Smart N., Franco-Viseras Mdel M., Rosario C.O., Swallow C.J., Dennis J.W., Riley P.R.
Nat. Cell Biol. 9:1131-1141(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-170.
[9]"The Cep63 paralogue Deup1 enables massive de novo centriole biogenesis for vertebrate multiciliogenesis."
Zhao H., Zhu L., Zhu Y., Cao J., Li S., Huang Q., Xu T., Huang X., Yan X., Zhu X.
Nat. Cell Biol. 15:1434-1444(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[10]"The Sak polo-box comprises a structural domain sufficient for mitotic subcellular localization."
Leung G.C., Hudson J.W., Kozarova A., Davidson A., Dennis J.W., Sicheri F.
Nat. Struct. Biol. 9:719-724(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 839-925, SUBUNIT, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA55748.
RefSeqNP_035625.2. NM_011495.2.
NP_775261.2. NM_173169.2.
UniGeneMm.3794.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1MBYX-ray2.00A/B839-925[»]
ProteinModelPortalQ64702.
SMRQ64702. Positions 1-309, 554-768, 845-919.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid203545. 5 interactions.
IntActQ64702. 6 interactions.
MINTMINT-1341538.

PTM databases

PhosphoSiteQ64702.

Proteomic databases

PRIDEQ64702.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000026858; ENSMUSP00000026858; ENSMUSG00000025758. [Q64702-1]
ENSMUST00000168287; ENSMUSP00000129134; ENSMUSG00000025758. [Q64702-3]
ENSMUST00000170825; ENSMUSP00000128916; ENSMUSG00000025758. [Q64702-2]
GeneID20873.
KEGGmmu:20873.
UCSCuc008pbm.1. mouse. [Q64702-2]
uc008pbo.1. mouse. [Q64702-1]
uc012cpc.1. mouse. [Q64702-3]

Organism-specific databases

CTD10733.
MGIMGI:101783. Plk4.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00530000062954.
HOVERGENHBG053617.
InParanoidQ80UT6.
KOK08863.
OMANIVSYER.
OrthoDBEOG7NCV33.
PhylomeDBQ64702.
TreeFamTF101090.

Enzyme and pathway databases

BRENDA2.7.11.21. 3474.

Gene expression databases

ArrayExpressQ64702.
BgeeQ64702.
CleanExMM_PLK4.
GenevestigatorQ64702.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000959. POLO_box_duplicated_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008266. Tyr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
PF00659. POLO_box. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50078. POLO_BOX. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ64702.
NextBio299719.
PROQ64702.
SOURCESearch...

Entry information

Entry namePLK4_MOUSE
AccessionPrimary (citable) accession number: Q64702
Secondary accession number(s): Q3UVA3 expand/collapse secondary AC list , Q6PEP6, Q78EG6, Q80UT6, Q8R0I5, Q9CVR6, Q9CVU6
Entry history
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: August 16, 2004
Last modified: April 16, 2014
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot