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serine/threonine protein kinase PLK4; polo-like kinase 4; PLK-4; serine/threonine protein kinase 18; serine/threonine protein kinase Sak (PLK4 SAK STK18)
Function:
- serine/threonine protein kinase
- 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, CP110, CEP135 & gamma-tubulin
- when overexpressed, PLK4 is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase
- role in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 & MDFIC & activate HAND1
- phosphorylates CDC25C & CHEK2/CHK2
- ubiquitinated, leading to its degradation by the proteasome
- Tyr-phosphorylated by TEC
- interacts with CEP152 (via N-terminus)
Structure:
- homodimer (putative)
- belongs to the protein kinase superfamily, Ser/Thr protein kinase family, CDC5/polo subfamily
- contains 1 POLO box domain
- contains 1 protein kinase domain
Compartment:
- cytoplasm, cytoskeleton, centrosome, centriole
- nucleus, nucleolus (putative)
- cleavage furrow [1]
- associates with centrioles throughout the cell cycle [2]
- not present at cleavage furrows [2]
Alternative splicing: named isoforms=3
Expression:
- down-regulated in HCT116 colorectal cancer cells, leading to aberrant centrioles composed of disorganized cylindrical microtubules & displaced appendages
- down-regulated by p53/TP53
Pathology:
- PLK4 role in tumorigenesis suggested by its role in centriole replication
General
serine/threonine kinase
Properties
SIZE: entity length = 970 aa
MW = 109 kD
COMPARTMENT: cytoplasm
cell nucleus
STATE: active state
MOTIF: kinase domain
SITE: 12-265
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 18-26
ATP-binding site
NAME: ATP-binding site
SITE: 41-41
aspartate residue {D136}
Tyr phosphorylation site {Y377}
Ser phosphorylation site {S378}
Ser phosphorylation site {S401}
Tyr phosphorylation site {Y420}
Ser phosphorylation site {S421}
Ser phosphorylation site {S499}
Thr phosphorylation site {T591}
Ser phosphorylation site {S592}
Ser phosphorylation site {S665}
Ser phosphorylation site {S671}
Ser phosphorylation site {S817}
POLO box domain {892-956}
Database Correlations
OMIM 605031
UniProt O00444
PFAM correlations
Entrez Gene 10733
Kegg hsa:10733
ENZYME 2.7.11.21
References
- UniProt :accession O00444
- Habedanck R et al
The Polo kinase Plk4 functions in centriole duplication.
Nat Cell Biol. 2005 Nov;7(11):1140-6.
PMID: 16244668