PLK4_DANRE
ID PLK4_DANRE Reviewed; 940 AA.
AC Q7ZVS3;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Serine/threonine-protein kinase PLK4 {ECO:0000250|UniProtKB:O00444};
DE EC=2.7.11.21 {ECO:0000250|UniProtKB:O00444};
DE AltName: Full=Polo-like kinase 4;
DE Short=PLK-4;
DE AltName: Full=Serine/threonine-protein kinase Sak;
GN Name=plk4 {ECO:0000250|UniProtKB:O00444}; Synonyms=sak;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=AB;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP DISRUPTION PHENOTYPE.
RX PubMed=25344692; DOI=10.1038/ng.3122;
RA Martin C.A., Ahmad I., Klingseisen A., Hussain M.S., Bicknell L.S.,
RA Leitch A., Nuernberg G., Toliat M.R., Murray J.E., Hunt D., Khan F.,
RA Ali Z., Tinschert S., Ding J., Keith C., Harley M.E., Heyn P., Mueller R.,
RA Hoffmann I., Daire V.C., Dollfus H., Dupuis L., Bashamboo A.,
RA McElreavey K., Kariminejad A., Mendoza-Londono R., Moore A.T., Saggar A.,
RA Schlechter C., Weleber R., Thiele H., Altmueller J., Hoehne W.,
RA Hurles M.E., Noegel A.A., Baig S.M., Nuernberg P., Jackson A.P.;
RT "Mutations in PLK4, encoding a master regulator of centriole biogenesis,
RT cause microcephaly, growth failure and retinopathy.";
RL Nat. Genet. 46:1283-1292(2014).
CC -!- FUNCTION: Serine/threonine-protein kinase that plays a central role in
CC centriole duplication. Able to trigger procentriole formation on the
CC surface of the parental centriole cylinder, leading to the recruitment
CC of centriole biogenesis proteins such as sass6, cenpj/cpap, ccp110,
CC cep135 and gamma-tubulin. When overexpressed, it is able to induce
CC centrosome amplification through the simultaneous generation of
CC multiple procentrioles adjoining each parental centriole during S
CC phase. Its central role in centriole replication suggests a possible
CC role in tumorigenesis, centrosome aberrations being frequently observed
CC in tumors. Also involved in deuterosome-mediated centriole
CC amplification in multiciliated that can generate more than 100
CC centrioles (By similarity). {ECO:0000250|UniProtKB:O00444}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.21;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.21;
CC -!- SUBUNIT: Homodimer. {ECO:0000250, ECO:0000250|UniProtKB:Q64702}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome, centriole {ECO:0000250|UniProtKB:O00444}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:O00444}. Note=Associates with centrioles
CC throughout the cell cycle. Component of the deuterosome, a structure
CC that promotes de novo centriole amplification in multiciliated cells
CC that can generate more than 100 centrioles (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated; leading to its degradation by the proteasome.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the gene results in a
CC smaller body size due to decreased cell proliferation. There is
CC evidence of a delay in mitotic progression with impaired centriole
CC duplication and impaired spindle formation. Mutant has a variable
CC reduction in eye size and impaired responses to visual stimuli
CC associated with a loss of cells containing cilia and an absence of
CC basal bodies in the photoreceptor layer. Knockdown mutant animals also
CC show a ciliary phenotype, with hydrocephalus, renal cysts, ventral
CC curvature, and left-right asymmetry defects.
CC {ECO:0000269|PubMed:25344692}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. CDC5/Polo subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159, ECO:0000255|PROSITE-ProRule:PRU01328,
CC ECO:0000255|PROSITE-ProRule:PRU01329}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BC045337; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; BC045337; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC045434; AAH45434.1; -; mRNA.
DR AlphaFoldDB; Q7ZVS3; -.
DR SMR; Q7ZVS3; -.
DR ComplexPortal; CPX-1300; CEP192-PLK4 complex.
DR ComplexPortal; CPX-1301; CEP152-PLK4 complex.
DR STRING; 7955.ENSDARP00000043865; -.
DR PaxDb; Q7ZVS3; -.
DR ZFIN; ZDB-GENE-030619-14; plk4.
DR eggNOG; KOG0575; Eukaryota.
DR InParanoid; Q7ZVS3; -.
DR PhylomeDB; Q7ZVS3; -.
DR Reactome; R-DRE-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-DRE-380259; Loss of Nlp from mitotic centrosomes.
DR Reactome; R-DRE-380270; Recruitment of mitotic centrosome proteins and complexes.
DR Reactome; R-DRE-380284; Loss of proteins required for interphase microtubule organization from the centrosome.
DR Reactome; R-DRE-380320; Recruitment of NuMA to mitotic centrosomes.
DR Reactome; R-DRE-5620912; Anchoring of the basal body to the plasma membrane.
DR Reactome; R-DRE-8854518; AURKA Activation by TPX2.
DR PRO; PR:Q7ZVS3; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005814; C:centriole; ISS:UniProtKB.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0098536; C:deuterosome; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0120098; C:procentriole; IC:ComplexPortal.
DR GO; GO:0120099; C:procentriole replication complex; IC:ComplexPortal.
DR GO; GO:0000922; C:spindle pole; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0098534; P:centriole assembly; IMP:ZFIN.
DR GO; GO:0007099; P:centriole replication; ISS:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; IMP:ZFIN.
DR GO; GO:0098535; P:de novo centriole assembly involved in multi-ciliated epithelial cell differentiation; ISS:UniProtKB.
DR GO; GO:0048589; P:developmental growth; IMP:ZFIN.
DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0046601; P:positive regulation of centriole replication; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0032465; P:regulation of cytokinesis; IBA:GO_Central.
DR CDD; cd13114; POLO_box_Plk4_1; 1.
DR CDD; cd13115; POLO_box_Plk4_2; 1.
DR CDD; cd13116; POLO_box_Plk4_3; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR033700; Plk4.
DR InterPro; IPR000959; POLO_box_dom.
DR InterPro; IPR033699; POLO_box_Plk4_1.
DR InterPro; IPR033698; POLO_box_Plk4_2.
DR InterPro; IPR033696; POLO_box_Plk4_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR PANTHER; PTHR24345:SF89; PTHR24345:SF89; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF18190; Plk4_PB1; 1.
DR Pfam; PF18409; Plk4_PB2; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51984; CPB1; 1.
DR PROSITE; PS51985; CPB2; 1.
DR PROSITE; PS50078; POLO_BOX; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cytoplasm; Cytoskeleton; Kinase; Nucleotide-binding;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Ubl conjugation.
FT CHAIN 1..940
FT /note="Serine/threonine-protein kinase PLK4"
FT /id="PRO_0000385282"
FT DOMAIN 12..265
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 563..676
FT /note="Cryptic POLO box 1 (CPB1)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01328"
FT DOMAIN 677..791
FT /note="Cryptic POLO box 2 (CPB2)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01329"
FT DOMAIN 863..927
FT /note="POLO box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00154"
FT REGION 262..353
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 409..529
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 262..314
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 326..351
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 439..467
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 478..517
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 136
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 18..26
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 41
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT CONFLICT 732
FT /note="D -> Y (in Ref. 1; BC045337)"
FT /evidence="ECO:0000305"
FT CONFLICT 870
FT /note="V -> A (in Ref. 1; BC045337)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 940 AA; 103485 MW; 558761963BCA649D CRC64;
MSVSIGDKIE DFKVLTLLGK GSFACVYRAK SVNTGLEVAI KMIDKKAMHK AGMVQRVINE
VEIQCRLKHP SVLELYNYFE DSNYVYLVLE MCHNGEMSRY LKERKNPFTE EEARHFMHQI
VKGMLYLHTH GIMHRDLTLT NLLLTTSMNI KIADFGLATQ LKLPSEKHFT MCGTPNYISP
EVATRSAHGL ESDVWSLGCM FYAFLTGRPP FDTDTVKRTL NKVVLGEYQM PMHISAEAQD
LIQQLLQKNP ALRPSLSAVL DHPFMTQSGP TASKDSGSSN GGSIDSGIAT ISTASNATNN
SSSSRLQRRT RQMIGQPLPS RMAPIPSHSH HSTSSSFKSG QDWQPNSQDD LSRMGVGRIP
VGADSGRPHS RYLRRAHSSD RSAVGYSHNP QEAELERCHS EEMLSGAGRL FPQTSGYRNA
PHGYSKHDRL PSPPVKQPAN PASSFSTSTH STRQQMPDSQ TQPWFSNDGV FKRPADMSGH
SSSGSFHSER GPIGTQTSCS DKPSGLHSQQ QPILFQHNNP GPCREDAFVS GHMSEPQAYS
DAQFPCPPLS KGKANTEKKD KVCLKKSFPP LCAARLKPIR QKTKNAVVSI LGNGEVCMEL
LKGQGAQERV KEVLRISCDG SMVTVYQPNE GKGFPVLDHP PSPPEDILIC SFDDLPEKYW
KKYQYATKFV QLVKSKTPKV TLYTKFAKCM LMENSPNPDL EVCFYDGAKT HKTSEQVRVV
EKSGKSYTVK GDVGLSGLNP ECRLYIELSE EGHRMCLSLE AAITAEEQRS AKNTPFFPIT
IGRRPVNPVP PAPAPSSSSS CRPAAAAEVA HVCLSPPQHP QITPSMISYA GSDLTTASVA
KGSSPVHKDE RTVNSGKVLK SIFVPNIGWV SQLTTGEVWV QFNDGSQLMV QVGVSCIIFT
SPEGHITRYK ENEKLPELVK EKLHCLSSIL GLLANPAARC
