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serine/threonine protein kinase greatwall; GW; GWL; hGWL; microtubule-associated serine/threonine protein kinase-like; MAST-L (MASTL, GW, GWL, THC2)
Function:
- serine/threonine kinase
- role in M phase by acting as a regulator of mitosis entry & maintenance
- acts by promoting inactivation of protein phosphatase 2A (PP2A) during M phase:
- does not directly inhibit PP2A but acts by mediating phosphorylation & subsequent activation of ARPP19 at Ser-62 & ENSA at Ser-67
- ARPP19 & ENSA are phosphatase inhibitors that specifically inhibit the PPP2R2D (PR55-delta) subunit of PP2A
- inactivation of PP2A during M phase is essential to keep cyclin B1-CDK1 activity high
- following DNA damage, MASTL is also involved in checkpoint recovery
- phosphorylates histone protein in vitro
- may be involved in megakaryocyte differentiation
- phosphorylation at Thr-741 by CDK1 during M phase activates its kinase activity (putative)
- maximum phosphorylation occurs in prometaphase
Structure:
- belongs to the protein kinase superfamily, AGC Ser/Thr protein kinase family
- contains 1 AGC-kinase C-terminal domain
- contains 1 protein kinase domain
Compartment:
- cytoplasm, cytoskeleton, centrosome, nucleus
- cleavage furrow
- during interphase is mainly nuclear
- upon nuclear envelope breakdown localizes in the cytoplasm & during mitosis at the centrosomes
- upon mitotic exit, moves to the cleavage furrow
Alternative splicing: named isoforms=3
Pathology:
- defects in MASTL are the cause of thrombocytopenia type 2
Notes:
- reduced levels of MASTL by RNAi
- causes a delay in G2 phase & slow chromosome condensation
- cells that enter & progress through mitosis often fail to completely separate their sister chromatids in anaphase leading to the formation of 4N G1 cells subsequent to failure of cytokinesis
General
serine/threonine kinase
Properties
SIZE: entity length = 879 aa
MW = 97 kD
COMPARTMENT: cytoplasm
nuclear membrane
STATE: active state
MOTIF: kinase domain
SITE: 35-835
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 41-49
ATP-binding site
NAME: ATP-binding site
SITE: 62-62
aspartate residue {D156}
Ser phosphorylation site {S293}
Ser phosphorylation site {S370}
Ser phosphorylation site {S452}
Ser phosphorylation site {S453}
Ser phosphorylation site {S512}
Ser phosphorylation site {S552}
Ser phosphorylation site {S556}
Ser phosphorylation site {S631}
Ser phosphorylation site {S657}
Ser phosphorylation site {S665}
Ser phosphorylation site {S668}
Tyr phosphorylation site {Y720}
Thr phosphorylation site {T722}
Ser phosphorylation site {S725}
Thr phosphorylation site {T741}
AGC-kinase C-terminal {836-879}
MOTIF: Ser phosphorylation site {S875}
Ser phosphorylation site {S878}
Database Correlations
OMIM correlations
MORBIDMAP 608221
UniProt Q96GX5
Pfam PF00069
Entrez Gene 84930
Kegg hsa:84930
ENZYME 2.7.11.1
References
- UniProt :accession Q96GX5
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/MASTL