MASTL

This gene encodes a microtubule-associated serine/threonine kinase. Mutations at this locus have been associated with autosomal dominant thrombocytopenia, also known as thrombocytopenia-2. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Feb 2010]

Full Name

Microtubule Associated Serine/Threonine Kinase Like

Function

Serine/threonine kinase that plays a key role in M phase by acting as a regulator of mitosis entry and maintenance. Acts by promoting the inactivation of protein phosphatase 2A (PP2A) during M phase: does not directly inhibit PP2A but acts by mediating phosphorylation and subsequent activation of ARPP19 and ENSA at 'Ser-62' and 'Ser-67', respectively. ARPP19 and 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, it is also involved in checkpoint recovery by being inhibited. Phosphorylates histone protein in vitro; however such activity is unsure in vivo. May be involved in megakaryocyte differentiation.

Biological Process

Cell division Source: UniProtKB-KW
Cellular response to DNA damage stimulus Source: UniProtKB
Female meiosis II Source: Ensembl
G2/M transition of mitotic cell cycle Source: UniProtKB
Intracellular signal transduction Source: GO_Central
Mitotic cell cycle Source: UniProtKB
Negative regulation of phosphoprotein phosphatase activity Source: UniProtKB
Peptidyl-serine phosphorylation Source: GO_Central
Positive regulation of ubiquitin protein ligase activity Source: Ensembl
Regulation of cell cycle Source: UniProtKB

Cellular Location

Cytoskeleton
centrosome
Nucleus
Other locations
Cleavage furrow
Note: During interphase is mainly nuclear, upon nuclear envelope breakdown localizes at the cytoplasm and during mitosis at the centrosomes. Upon mitotic exit moves to the cleavage furrow.

Involvement in disease

Defects in MASTL may play a role in the pathogenesis of thrombocytopenia, a disorder defined by reduced number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting.

PTM

Phosphorylation at Thr-741 by CDK1 during M phase activates its kinase activity (By similarity). Maximum phosphorylation occurs in prometaphase.