{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"O00444","secondaryAccessions":["B2RAL0","B7Z837","B7Z8G7","Q8IYF0","Q96Q95","Q9UD84","Q9UDE2"],"uniProtkbId":"PLK4_HUMAN","entryAudit":{"firstPublicDate":"2004-08-16","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2007-11-13","entryVersion":214,"sequenceVersion":3},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Serine/threonine-protein kinase PLK4"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16244668"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18239451"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19164942"}],"value":"2.7.11.21"}]},"alternativeNames":[{"fullName":{"value":"Polo-like kinase 4"},"shortNames":[{"value":"PLK-4"}]},{"fullName":{"value":"Serine/threonine-protein kinase 18"}},{"fullName":{"value":"Serine/threonine-protein kinase Sak"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:11397"}],"value":"PLK4"},"synonyms":[{"value":"SAK"},{"value":"STK18"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16244668"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16326102"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17681131"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18239451"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19164942"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21725316"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22020124"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27796307"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30804208"}],"value":"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, 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. 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. Phosphorylates CDC25C and CHEK2. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification (PubMed:22020124). Phosphorylates CEP131 at 'Ser-78' and PCM1 at 'Ser-372' which is essential for proper organization and integrity of centriolar satellites (PubMed:30804208)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:17989"},{"database":"Rhea","id":"RHEA-COMP:9863"},{"database":"Rhea","id":"RHEA-COMP:11604"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:29999"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:83421"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.11.21","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16244668"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18239451"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19164942"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:46608"},{"database":"Rhea","id":"RHEA-COMP:11060"},{"database":"Rhea","id":"RHEA-COMP:11605"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30013"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:61977"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.11.21","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16244668"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18239451"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19164942"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q64702"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20852615"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21059844"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27246242"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30804208"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32107292"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32433990"}],"value":"Homodimer (By similarity). Interacts with CEP152 (via N-terminus). Interacts with CEP78; this interaction may be important for proper PLK4 localization to the centriole and PLK4-induced overduplication of centrioles (PubMed:27246242). Interacts with CEP131 (PubMed:30804208). Interacts simultaneously with TENT5C and CEP192 (PubMed:32433990). Interacts with TENT5C; this interaction leads to the TENT5C recruitment in the centrosome (PubMed:32433990). Interacts with CEP85; this interaction may be important in cell migration and centriole assembly (PubMed:32107292)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"Q9NX04","geneName":"AIRIM","intActId":"EBI-8643161"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"P36575","geneName":"ARR3","intActId":"EBI-718116"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"Q9Y297","geneName":"BTRC","intActId":"EBI-307461"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"A6NKD9","geneName":"CCDC85C","intActId":"EBI-2561671"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"O94986","geneName":"CEP152","intActId":"EBI-311012"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"O94986-3","geneName":"CEP152","intActId":"EBI-15878364"},"numberOfExperiments":16,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"Q8TEP8","geneName":"CEP192","intActId":"EBI-2339778"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"Q8TEP8-3","geneName":"CEP192","intActId":"EBI-16111881"},"numberOfExperiments":13,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"P59910","geneName":"DNAJB13","intActId":"EBI-11514233"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"Q9H8V3","geneName":"ECT2","intActId":"EBI-1054039"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"Q14241","geneName":"ELOA","intActId":"EBI-742350"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"O95995","geneName":"GAS8","intActId":"EBI-1052570"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"Q9H4L5","geneName":"OSBPL3","intActId":"EBI-1051317"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"P07237","geneName":"P4HB","intActId":"EBI-395883"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"O00444","geneName":"PLK4","intActId":"EBI-746202"},"numberOfExperiments":10,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"P31947","geneName":"SFN","intActId":"EBI-476295"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"Q96R06","geneName":"SPAG5","intActId":"EBI-413317"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"Q15468","geneName":"STIL","intActId":"EBI-7488405"},"numberOfExperiments":11,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"Q96A09","geneName":"TENT5B","intActId":"EBI-752030"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"Q9UBB9","geneName":"TFIP11","intActId":"EBI-1105213"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"Q9BYV2","geneName":"TRIM54","intActId":"EBI-2130429"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"P62258","geneName":"YWHAE","intActId":"EBI-356498"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O00444","intActId":"EBI-746202"},"interactantTwo":{"uniProtKBAccession":"Q04917","geneName":"YWHAH","intActId":"EBI-306940"},"numberOfE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Associates with centrioles throughout the cell cycle. According to PubMed:16244668, it is not present at cleavage furrows"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22020124"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27246242"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27796307"}],"value":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole","id":"SL-0046"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q64702"}],"value":"Nucleus, nucleolus","id":"SL-0188"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q64702"}],"value":"Cleavage furrow","id":"SL-0467"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30804208"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32433990"}],"value":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome","id":"SL-0048"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["O00444-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["O00444-2"],"sequenceIds":["VSP_038117"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["O00444-3"],"sequenceIds":["VSP_038116"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15967108"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19454482"}],"value":"Down-regulated in HCT 116 colorectal cancer cells, leading to aberrant centrioles composed of disorganized cylindrical microtubules and displaced appendages. Down-regulated by p53/TP53"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32433990"}],"value":"Cryptic POLO box 1 (CPB1) and Cryptic POLO box 2 (CPB2) domains can simultaneously bind to both TENT5C and CEP192"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27796307"}],"value":"Acetylation by KAT2A and KAT2B impairs kinase activity by shifting the kinase to an inactive conformation"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q64702"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36590171"}],"value":"Ubiquitinated; leading to its degradation by the proteasome (By similarity). 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